Traumatic Brain Injury (TBI)

Terahertz biotechnology has been increasingly applied in various biomedical fields and has especially shown great potential for application in brain sciences. In this article, we review the development of terahertz biotechnology and its applications in the field of neuropsychiatry. Available evidence indicates promising prospects for the use of terahertz spectroscopy and terahertz imaging techniques in the diagnosis of amyloid disease, cerebrovascular disease, glioma, psychiatric disease, traumatic brain injury, and myelin deficit. In vitro and animal experiments have also demonstrated the potential therapeutic value of terahertz technology in some neuropsychiatric diseases. Although the precise underlying mechanism of the interactions between terahertz electromagnetic waves and the biosystem is not yet fully understood, the research progress in this field shows great potential for biomedical noninvasive diagnostic and therapeutic applications. However, the biosafety of terahertz radiation requires further exploration regarding its two-sided efficacy in practical applications. This review demonstrates that terahertz biotechnology has the potential to be a promising method in the field of neuropsychiatry based on its unique advantages.

Dysfunction of the central nervous system (CNS) following traumatic brain injuries (TBI), spinal cord injuries (SCI), or strokes remains challenging to address using existing medications and cell-based therapies. Although therapeutic cell administration, such as stem cells and neuronal progenitor cells (NPCs), have shown promise in regenerative properties, they have failed to provide substantial benefits. However, the development of living cortical tissue engineered grafts, created by encapsulating these cells within an extracellular matrix (ECM) mimetic hydrogel scaffold, presents a promising functional replacement for damaged cortex in cases of stroke, SCI, and TBI. These grafts facilitate neural network repair and regeneration following CNS injuries. Given that natural glycosaminoglycans (GAGs) are a major constituent of the CNS, GAG-based hydrogels hold potential for the next generation of CNS healing therapies and in vitro modeling of CNS diseases. Brain-specific GAGs not only offer structural and biochemical signaling support to encapsulated neural cells but also modulate the inflammatory response in lesioned brain tissue, facilitating host integration and regeneration. This review briefly discusses different roles of GAGs and their related proteoglycan counterparts in healthy and diseases brain and explores current trends and advancements in GAG-based biomaterials for treating CNS injuries and modeling diseases. Additionally, it examines injectable, 3D bioprintable, and conductive GAG-based scaffolds, highlighting their clinical potential for in vitro modeling of patient-specific neural dysfunction and their ability to enhance CNS regeneration and repair following CNS injury in vivo.

Traumatic brain injury (TBI) causes a prolonged inflammatory response in the central nervous system (CNS) driven by microglia. Microglial reactivity is exacerbated by stress, which often provokes sleep disturbances. We have previously shown that sleep fragmentation (SF) stress after experimental TBI increases microglial reactivity and impairs hippocampal function 30 days post-injury (DPI). The neuroimmune response is highly dynamic the first few weeks after TBI, which is also when injury induced sleep-wake deficits are detected. Therefore, we hypothesized that even a few weeks of TBI SF stress would synergize with injury induced sleep-wake deficits to promote neuroinflammation and impair outcome. Here, we investigated the effects of environmental SF in a lateral fluid percussion model of mouse TBI. Half of the mice were undisturbed, and half were exposed to 5 h of SF around the onset of the light cycle, daily, for 14 days. All mice were then undisturbed 15-30 DPI, providing a period for SF stress recovery (SF-R). Mice exposed to SF stress slept more than those in control housing 7-14 DPI and engaged in more total daily sleep bouts during the dark period. However, SF stress did not exacerbate post-TBI sleep deficits. Testing in the Morris water maze revealed sex dependent differences in spatial reference memory 9-14 DPI with males performing worse than females. Post-TBI SF stress suppressed neurogenesis-related gene expression and increased inflammatory signaling in the cortex at 14 DPI. No differences in sleep behavior were detected between groups during the SF stress recovery period 15-30 DPI. Microscopy revealed cortical and hippocampal IBA1 and CD68 percent-area increased in TBI SF-R mice 30 DPI. Additionally, neuroinflammatory gene expression was increased, and synaptogenesis-related gene expression was suppressed in TBI-SF mice 30 DPI. Finally, IPA canonical pathway analysis showed post-TBI SF impaired and delayed activation of synapse-related pathways between 14 and 30 DPI. These data show that transient SF stress after TBI impairs recovery and conveys long-lasting impacts on neuroimmune function independent of continuous sleep deficits. Together, these finding support that even limited exposure to post-TBI SF stress can have lasting impacts on cognitive recovery and regulation of the immune response to trauma.

To examine challenges in return to work (RTW) for persons with persistent postconcussion symptoms (PPCS) experienced by the affected employees and their managers.

To examine the safety of cardiorespiratory fitness (CRF) assessment and training in the early sub-acute phase of recovery (≤3 months) following moderate-to-extremely severe traumatic brain injury (TBI).

This article reviews the mechanisms of primary traumatic injury to the brain and spinal cord, with an emphasis on grading severity, identifying surgical indications, anticipating complications, and managing secondary injury.

We compared the emergency department (ED) evaluation and outcomes of young head-injured infants to older children.

Alcohol withdrawal syndrome (AWS) presents with a complex spectrum of clinical manifestations that complicate postoperative management. In trauma setting, subjective screening for AWS remains challenging due to the criticality of injury in these patients. We thus identified several patient characteristics and perioperative outcomes associated AWS development.

Biomarkers of neuronal, glial cells and inflammation in traumatic brain injury (TBI) are available but they do not specifically reflect the damage to synapses, which represent the bulk volume of the brain. Experimental models have demonstrated extensive involvement of synapses in acute TBI, but biomarkers of synaptic damage in human patients have not been explored.

Chronic pain after traumatic brain injury (TBI) is prevalent and associated with poor outcomes. By providing multidisciplinary care through expert consultation, a collaborative care (CC) treatment approach may reduce pain interference.

Mild traumatic brain injury (mTBI) has emerged as a potential risk factor for the development of neurodegenerative conditions such as Alzheimer's disease and chronic traumatic encephalopathy. Blast mTBI, caused by exposure to a pressure wave from an explosion, is predominantly experienced by military personnel and has increased in prevalence and severity in recent decades. Yet the underlying pathology of blast mTBI is largely unknown. We examined the expression and localization of AQP4 in human post-mortem frontal cortex and observed distinct laminar differences in AQP4 expression following blast exposure. We also observed similar laminar changes in AQP4 expression and localization and delayed impairment of glymphatic function that emerged 28 days following blast injury in a mouse model of repetitive blast mTBI. In a cohort of veterans with blast mTBI, we observed that blast exposure was associated with an increased burden of frontal cortical MRI-visible perivascular spaces, a putative neuroimaging marker of glymphatic perivascular dysfunction. These findings suggest that changes in AQP4 and delayed glymphatic impairment following blast injury may render the post-traumatic brain vulnerable to post-concussive symptoms and chronic neurodegeneration.

Cross-sectional study.

This study aimed to investigate the effects of focal brain cooling (FBC) on spreading depolarization (SD), which is associated with several neurological disorders. Although it has been studied from various aspects, no medication has been developed that can effectively control SD. As FBC can reduce neuronal damage and promote functional recovery in pathological conditions such as epilepsy, cerebral ischemia, and traumatic brain injury, it may also potentially suppress the onset and progression of SD. We created an experimental rat model of SD by administering 1 M potassium chloride (KCl) to the cortical surface. Changes in neuronal and vascular modalities were evaluated using multimodal recording, which simultaneously recorded brain temperature (BrT), wide range electrocorticogram, and two-dimensional cerebral blood flow. The rats were divided into two groups (cooling [CL] and non-cooling [NC]). Warm or cold saline was perfused on the surface of one hemisphere to maintain BrT at 37°C or 15°C in the NC and CL groups, respectively. Western blot analysis was performed to determine the effects of FBC on endothelial nitric oxide synthase (eNOS) expression. In the NC group, KCl administration triggered repetitive SDs (mean frequency = 11.57/h). In the CL group, FBC increased the duration of all KCl-induced events and gradually reduced their frequency. Additionally, eNOS expression decreased in the cooled brain regions compared to the non-cooled contralateral hemisphere. The results obtained by multimodal recording suggest that FBC suppresses SD and decreases eNOS expression. This study may contribute to developing new treatments for SD and related neurological disorders.

Controlling elevated intracranial pressure following brain injury with hyperosmolar agents is one of the mainstay treatments in traumatic brain injury patients. In this study, we compared the effects of hypertonic saline (HS) and mannitol in reducing increased intracranial pressure.

Growth factor-derived peptides are bioactive molecules that play a crucial role in various physiological processes within the human body. Over the years, extensive research has revealed their diverse applications, ranging from antimicrobial properties to their potential in neuroprotection and treating various diseases. These peptides exhibit innate immune responses and have been found to possess potent antimicrobial properties against a wide range of pathogens. Growth factor-derived peptides have demonstrated the ability to promote neuronal survival, prevent cell death, and stimulate neural regeneration. As a result, they hold immense promise in the treatment of various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, as well as in the management of traumatic brain injuries. Moreover, growth factor-derived peptides have shown potential for supporting tissue repair and wound healing processes. By enhancing cell proliferation and migration, these peptides contribute to the regeneration of damaged tissues and promote a more efficient healing response. The applications of growth factor-derived peptides extend beyond their therapeutic potential in health; they also have a role in various disease conditions. For example, researchers have explored their influence on cancer cells, where some peptides have demonstrated anti-cancer properties, inhibiting tumor growth and promoting apoptosis in cancer cells. Additionally, their immunomodulatory properties have been investigated for potential applications in autoimmune disorders. Despite the immense promise shown by growth factor-derived peptides, some challenges need to be addressed. Nevertheless, ongoing research and advancements in biotechnology offer promising avenues to overcome these obstacles. The review summarizes the foundational biology of growth factors and the intricate signaling pathways in various physiological processes as well as diseases such as cancer, neurodegenerative disorders, cardiovascular ailments, and metabolic syndromes.

Mild traumatic brain injury (mTBI) or concussion is prevalent among trauma patients, but symptoms vary. Assessing discharge safety is not standardized. At our institution, occupational therapy (OT) performs cognitive assessments for mTBI to determine discharge readiness, potentially increasing resource utilization. We aimed to describe characteristics and outcomes in mTBI trauma patients and hypothesized that OT consultation was associated with increased length of stay (LOS).

This report emphasizes the significance of acknowledging infrequent yet severe complications such as bowel perforation and transanal protrusion post ventriculoperitoneal shunt (VPS) surgery. VPS patients should be observed for atypical indicators and manifestations that could suggest the presence of such complications, even in the lack of traditional clinical signs of peritonitis or bowel perforation.

The brain glymphatic system is currently being explored in the context of many neurological disorders and diseases, including traumatic brain injury, Alzheimer's disease, and ischemic stroke. However, little is known about the impact of brain tumors on glymphatic function. Mechanical forces generated during tumor development and growth may be responsible for compromised glymphatic transport pathways, reducing waste clearance and cerebrospinal fluid (CSF) transport in the brain parenchyma. One such force is solid stress, i.e., growth-induced forces from cell hyperproliferation and excess matrix deposition. Because there are no prior studies assessing the impact of tumor-derived solid stress on glymphatic system structure and performance in the brain parenchyma, this study serves to fill an important gap in the field.

Upper and lower limb spasticity is commonly associated with central nervous system disorders including stroke, traumatic brain injury, multiple sclerosis, cerebral palsy, and spinal cord injury, but little is known about the concurrent treatment of upper and lower limb spasticity with botulinum toxins.

Traditional neuroimaging methods have identified alterations in brain activity patterns following mild traumatic brain injury (mTBI), particularly during rest, complex tasks, and normal vision. However, studies using graph theory to examine brain network changes in mTBI have produced varied results, influenced by the specific networks and task demands analyzed. In our study, we employed functional MRI to observe 17 mTBI patients and 54 healthy individuals as they viewed a simple, non-narrative underwater film, simulating everyday visual tasks. This approach revealed significant mTBI-related changes in network connectivity, efficiency, and organization. Specifically, the mTBI group exhibited higher overall connectivity and local network specialization, suggesting enhanced information integration without overwhelming the brain's processing capabilities. Conversely, these patients showed reduced network segregation, indicating a less compartmentalized brain function compared to healthy controls. These patterns were consistent across various visual cortex subnetworks, except in primary visual areas. Our findings highlight the potential of using naturalistic stimuli in graph-based neuroimaging to understand brain network alterations in mTBI and possibly other conditions affecting brain integration.

Background Low-level light therapy (LLLT) has been shown to modulate recovery in patients with traumatic brain injury (TBI). However, the impact of LLLT on the functional connectivity of the brain when at rest has not been well studied. Purpose To use functional MRI to assess the effect of LLLT on whole-brain resting-state functional connectivity (RSFC) in patients with moderate TBI at acute (within 1 week), subacute (2-3 weeks), and late-subacute (3 months) recovery phases. Materials and Methods This is a secondary analysis of a prospective single-site double-blinded sham-controlled study conducted in patients presenting to the emergency department with moderate TBI from November 2015 to July 2019. Participants were randomized for LLLT and sham treatment. The primary outcome of the study was to assess structural connectivity, and RSFC was collected as the secondary outcome. MRI was used to measure RSFC in 82 brain regions in participants during the three recovery phases. Healthy individuals who did not receive treatment were imaged at a single time point to provide control values. The Pearson correlation coefficient was estimated to assess the connectivity strength for each brain region pair, and estimates of the differences in Fisher -transformed correlation coefficients (hereafter, differences) were compared between recovery phases and treatment groups using a linear mixed-effects regression model. These analyses were repeated for all brain region pairs. False discovery rate (FDR)-adjusted values were computed to account for multiple comparisons. Quantile mixed-effects models were constructed to quantify the association between the Rivermead Postconcussion Symptoms Questionnaire (RPQ) score, recovery phase, and treatment group. Results RSFC was evaluated in 17 LLLT-treated participants (median age, 50 years [IQR, 25-67 years]; nine female), 21 sham-treated participants (median age, 50 years [IQR, 43-59 years]; 11 female), and 23 healthy control participants (median age, 42 years [IQR, 32-54 years]; 13 male). Seven brain region pairs exhibited a greater change in connectivity in LLLT-treated participants than in sham-treated participants between the acute and subacute phases (range of differences, 0.37 [95% CI: 0.20, 0.53] to 0.45 [95% CI: 0.24, 0.67]; FDR-adjusted value range, .010-.047). Thirteen different brain region pairs showed an increase in connectivity in sham-treated participants between the subacute and late-subacute phases (range of differences, 0.17 [95% CI: 0.09, 0.25] to 0.26 [95% CI: 0.14, 0.39]; FDR-adjusted value range, .020-.047). There was no evidence of a difference in clinical outcomes between LLLT-treated and sham-treated participants (range of differences in medians, -3.54 [95% CI: -12.65, 5.57] to -0.59 [95% CI: -7.31, 8.49]; value range, .44-.99), as measured according to RPQ scores. Conclusion Despite the small sample size, the change in RSFC from the acute to subacute phases of recovery was greater in LLLT-treated than sham-treated participants, suggesting that acute-phase LLLT may have an impact on resting-state neuronal circuits in the early recovery phase of moderate TBI. ClinicalTrials.gov Identifier: NCT02233413 © RSNA, 2024

Visualization of human brain activity is crucial for understanding normal and aberrant brain function. Currently available neural activity recording methods are highly invasive, have low sensitivity, and cannot be conducted outside of an operating room. Functional ultrasound imaging (fUSI) is an emerging technique that offers sensitive, large-scale, high-resolution neural imaging; however, fUSI cannot be performed through the adult human skull. Here, we used a polymeric skull replacement material to create an acoustic window compatible with fUSI to monitor adult human brain activity in a single individual. Using an in vitro cerebrovascular phantom to mimic brain vasculature and an in vivo rodent cranial defect model, first, we evaluated the fUSI signal intensity and signal-to-noise ratio through polymethyl methacrylate (PMMA) cranial implants of different thicknesses or a titanium mesh implant. We found that rat brain neural activity could be recorded with high sensitivity through a PMMA implant using a dedicated fUSI pulse sequence. We then designed a custom ultrasound-transparent cranial window implant for an adult patient undergoing reconstructive skull surgery after traumatic brain injury. We showed that fUSI could record brain activity in an awake human outside of the operating room. In a video game "connect the dots" task, we demonstrated mapping and decoding of task-modulated cortical activity in this individual. In a guitar-strumming task, we mapped additional task-specific cortical responses. Our proof-of-principle study shows that fUSI can be used as a high-resolution (200 μm) functional imaging modality for measuring adult human brain activity through an acoustically transparent cranial window.

 Absent pupillary reaction occasionally heralds a poor prognosis following severe head injury. The purpose of the study was to evaluate the outcome of all patients who underwent acute evacuation of epidural hematoma (EDH) despite absent bilateral pupillary reaction.

The purpose of this study was to determine the extent to which patient's perspective of symptom improvement, as indexed by the Patient Global Impression of Change (PGIC) survey, is associated with symptom improvement on common measures of neurobehavioral and mental health symptoms following concussion.

Traumatic brain injury (TBI) is often followed by post-traumatic epilepsy (PTE), a condition often difficult to treat and leading to a substantial decline in quality of life as well as increased long-term mortality. The latent period between TBI and the emergence of spontaneous recurrent seizures provides an opportunity for pharmacological intervention to prevent epileptogenesis. Biomarkers capable of predicting PTE development are urgently needed to facilitate clinical trials of putative anti-epileptogenic drugs. EEG is a widely available and flexible diagnostic modality that plays a fundamental role in epileptology. We systematically review the advances in the field of the discovery of EEG biomarkers for the prediction of PTE in humans. Despite recent progress, the field faces several challenges including short observation periods, a focus on early post-injury monitoring, difficulties in translating findings from animal models to scalp EEG, and emerging evidence indicating the importance of assessing altered background scalp EEG activity alongside epileptiform activity using quantitative EEG methods while also considering sleep abnormalities in future studies.

Traumatic brain injury (TBI) occurs at the highest rate in older adulthood and increases risk for cognitive impairment and dementia.

Dendrites are injured in a variety of clinical conditions such as traumatic brain and spinal cord injuries and stroke. How neurons detect injury directly to their dendrites to initiate a pro-regenerative response has not yet been thoroughly investigated. Calcium plays a critical role in the early stages of axonal injury detection and is also indispensable for regeneration of the severed axon. Here, we report cell and neurite type-specific differences in laser injury-induced elevations of intracellular calcium levels. Using a human KCNJ2 transgene, we demonstrate that hyperpolarizing neurons only at the time of injury dampens dendrite regeneration, suggesting that inhibition of injury-induced membrane depolarization (and thus early calcium influx) plays a role in detecting and responding to dendrite injury. In exploring potential downstream calcium-regulated effectors, we identify L-type voltage-gated calcium channels, inositol triphosphate signaling, and protein kinase D activity as drivers of dendrite regeneration. In conclusion, we demonstrate that dendrite injury-induced calcium elevations play a key role in the regenerative response of dendrites and begin to delineate the molecular mechanisms governing dendrite repair.

Repeated mild head injuries due to sports, or domestic violence and military service are increasingly linked to debilitating symptoms in the long term. Although symptoms may take decades to manifest, potentially treatable neurobiological alterations must begin shortly after injury. Better means to diagnose and treat traumatic brain injuries, requires an improved understanding of the mechanisms underlying progression and means through which they can be measured. Here, we employ a repetitive mild closed-head injury (rmTBI) and chronic variable stress (CVS) mouse model to investigate emergent structural and functional brain abnormalities. Brain imaging is achieved with [ F]SynVesT-1 positron emission tomography, with the synaptic vesicle glycoprotein 2A ligand marking synapse density and BOLD (blood-oxygen-level-dependent) functional magnetic resonance imaging (fMRI). Animals were scanned six weeks after concluding rmTBI/Stress procedures. Injured mice showed widespread in synaptic density coupled with an i in local BOLD-fMRI synchrony detected as regional homogeneity. Injury-affected regions with synapse density showed a in fMRI regional homogeneity. Taken together, these observations may reflect compensatory mechanisms following injury. Multimodal studies are needed to provide deeper insights into these observations.

Following mild traumatic brain injury (mTBI), children show reduced processing speed (PS). Evidence suggests that slowed PS after TBI is associated with working memory deficits. Our aim was to investigate several forms of PS and to examine its impact on working and episodic memory performance in children after mTBI.

The Endothelial Activation and Stress Index (EASIX) is a novel marker of endothelial injury and correlates with survival of various patients. The endothelial dysfunction plays an important role on the pathophysiological process of traumatic brain injury (TBI). This study was designed to explore the prognostic value of EASIX on TBI patients.

Severe traumatic brain injury (sTBI) induced neuronal loss and brain atrophy contribute significantly to long-term disabilities. Brain extracellular matrix (ECM) associated chondroitin sulfate (CS) glycosaminoglycans promote neural stem cell (NSC) maintenance, and CS hydrogel implants have demonstrated the ability to enhance neuroprotection, in preclinical sTBI studies. However, the ability of neuritogenic chimeric peptide (CP) functionalized CS hydrogels in promoting functional recovery, after controlled cortical impact (CCI) and suction ablation (SA) induced sTBI, has not been previously demonstrated. We hypothesized that neuritogenic (CS)CP hydrogels will promote neuritogenesis of human NSCs, and accelerate brain tissue repair and functional recovery in sTBI rats.

Epilepsy is one of the most common neurological diseases. Epileptic seizures very often result in head injuries that may lead to many adverse consequences, both acute and chronic. They contribute to the need for hospitalization, modification of treatment, and a general decline in social productivity. The objective of our review is to characterize and assess management aspects of seizure-related head injuries (SRHIs) as an important and frequent clinical problem present in emergency department settings. PubMed and other relevant databases and websites were systematically searched for articles on traumatic brain injuries connected with the occurrence of seizures published from inception to 9 April 2024; then, we reviewed the available literature. Our review showed that SRHIs can lead to various acute complications, in some cases requiring hospitalization and neurosurgical intervention. Long-term complications and cognitive decline after injury might be present, eventually implying a negative impact on a patient's quality of life. Despite being frequent and clinically important, there are still no widely accepted, uniform recommendations for the management of patients with SRHIs. As such, a concise and standardized protocol for the management of seizure-related head injuries in emergency departments is worth consideration.

We examined spatial patterns of brain atrophy after mild, moderate, and severe traumatic brain injury (TBI), the relationship between progression of brain atrophy with initial traumatic axonal injury (TAI), cognitive outcome, and with serum biomarkers of brain injury.

The kallikrein-kinin system is one of the first inflammatory pathways to be activated following traumatic brain injury (TBI) and has been shown to exacerbate brain edema formation in the acute phase through activation of Bradykinin-2-receptors (B2R). However, the influence of B2 receptors on chronic posttraumatic damage and outcome is unclear. In the current study we assessed long term effects of B2R-knockout after experimental traumatic brain injury. B2R knockout mice (heterozygous, homozygous) and wildtype littermates (n=10/group) were subjected to controlled cortical impact TBI. Lesion size was evaluated by MRI up to 90 days after CCI. Motor and memory function were regularly assessed by Neurological severity Score (NSS), Beam Walk (BW), and Barnes Maze test. 90 days after TBI, brains were harvested for immunohistochemical analysis. There was no difference in cortical lesion size between B2R deficient and wildtype animals three months after injury, however, hippocampal damage was reduced in B2R KO mice (p=0.03). Protection of hippocampal tissue was accompanied by a significant improvement of learning and memory function three months after TBI (p=0.02 WT vs. KO), whereas motor function was not influenced. Scar formation and astrogliosis were unaffected, but bradykinin-2-receptor deficiency led to a gene-dose dependent attenuation of microglial activation and a reduction of CD45+ cells three months after TBI in cortex (p=0.0003) and hippocampus (p< 0.0001). These results suggest that chronic hippocampal neurodegeneration and subsequent cognitive impairment is mediated by prolonged neuroinflammation and bradykinin-2-receptors. Inhibition of B2-receptors may therefore represent a novel strategy to reduce long-term neurocognitive deficits after TBI.

This study aimed to assess the prevalence of neuropsychiatric sequelae following traumatic brain injury (TBI) among the Western Asian, South Asian and African regions of the global south. All studies on psychiatric disturbances or cognitive impairment following TBI conducted (until August 2021) in the 83 countries that constitute the aforementioned regions were reviewed; 6 databases were selected for the literature search. After evaluating the articles using the Joanna Briggs Institute guidelines, the random effects model was used to estimate the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD), TBI-related sleep disturbance (TBI-SD), obsessive-compulsive disorder (OCD) and cognitive impairment. Of 56 non-duplicated studies identified in the initial search, 27 were eligible for systematic review and 23 for meta-analysis. The pooled prevalence of depression in 1,882 samples was 35.35%, that of anxiety in 1,211 samples was 28.64%, that of PTSD in 426 samples was 19.94%, that of OCD in 313 samples was 19.48%, that of TBI-SD in 562 samples was 26.67% and that of cognitive impairment in 941 samples was 49.10%. To date, this is the first critical review to examine the spectrum of post-TBI neuropsychiatric sequelae in the specified regions. Although existing studies lack homogeneous data due to variability in the diagnostic tools and outcome measures utilised, the reported prevalence rates are significant and comparable to statistics from the global north.

Level-I and level-II trauma centers are required to offer equivalent resources since "The Orange Book." This study evaluates differences between level-I and level-II management of solid organ injury (SOI) with traumatic brain injury (TBI).

Neurostimulation protocols are increasingly used as therapeutic interventions, including for brain injury. In addition to the direct activation of neurons, these stimulation protocols are also likely to have downstream effects on those neurons' synaptic outputs. It is well known that alterations in the strength of synaptic connections (long-term potentiation, LTP; long-term depression, LTD) are sensitive to the frequency of stimulation used for induction, however little is known about the contribution of the temporal pattern of stimulation to the downstream synaptic plasticity that may be induced by neurostimulation in the injured brain. We explored interactions of the temporal pattern and frequency of neurostimulation in the normal cerebral cortex and after mild traumatic brain injury (mTBI), to inform therapies to strengthen or weaken neural circuits in injured brains, as well as to better understand the role of these factors in normal brain plasticity. Whole-cell (WC) patch-clamp recordings of evoked postsynaptic potentials (PSPs) in individual neurons, as well as field potential (FP) recordings, were made from layer 2/3 of visual cortex in response to stimulation of layer 4, in acute slices from control (naïve), sham operated, and mTBI rats. We compared synaptic plasticity induced by different stimulation protocols, each consisting of a specific frequency (1 Hz, 10 Hz, or 100 Hz), continuity (continuous or discontinuous), and temporal pattern (perfectly regular, slightly irregular, or highly irregular). At the individual neuron level, dramatic differences in plasticity outcome occurred when the highly irregular stimulation protocol was used at 1 Hz or 10 Hz, producing an overall LTD in controls and shams, but a robust overall LTP after mTBI. Consistent with the individual neuron results, the plasticity outcomes for simultaneous FP recordings were similar, indicative of our results generalizing to a larger scale synaptic network than can be sampled by individual WC recordings alone. In addition to the differences in plasticity outcome between control (naïve or sham) and injured brains, the dynamics of the changes in synaptic responses that developed during stimulation were predictive of the final plasticity outcome. Our results demonstrate that the temporal pattern of stimulation plays a role in the polarity and magnitude of synaptic plasticity induced in the cerebral cortex while highlighting differences between normal and injured brain responses. Moreover, these results may be useful for optimization of neurostimulation therapies to treat mTBI and other brain disorders, in addition to providing new insights into downstream plasticity signaling mechanisms in the normal brain.

Brain tissue injury caused by mild traumatic brain injury (mTBI) disproportionately concentrates in the midbrain, cerebellum, mesial temporal lobe, and the interface between cortex and white matter at sulcal depths. The bio-mechanical principles that explain why physical impacts to different parts of the skull translate to common foci of injury concentrated in specific brain structures are unknown. A general and longstanding idea, which has not to date been directly tested in humans, is that different brain regions are differentially susceptible to strain loading. We use Magnetic Resonance Elastography (MRE) in healthy participants to develop whole-brain bio-mechanical vulnerability maps that independently define which regions of the brain exhibit disproportionate strain concentration. We then validate those vulnerability maps in a prospective cohort of mTBI patients, using diffusion MRI data collected at three cross-sectional timepoints after injury: acute, sub-acute, chronic. We show that regions that exhibit high strain, measured with MRE, are also the sites of greatest injury, as measured with diffusion MR in mTBI patients. This was the case in acute, subacute, and chronic subgroups of the mTBI cohort. Follow-on analyses decomposed the biomechanical cause of increased strain by showing it is caused jointly by disproportionately higher levels of energy arriving to high-strain structures, as well as the inability of high-strain structures to effectively disperse that energy. These findings establish a causal mechanism that explains the anatomy of injury in mTBI based on in vivo rheological properties of the human brain.

Repetitive mild traumatic brain injury (rmTBI) often occurs in individuals engaged in contact sports, particularly boxing. This study aimed to elucidate the effects of rmTBI on phase-locking value (PLV)-based graph theory and functional network architecture in individuals with boxing-related injuries in five frequency bands by employing resting-state electroencephalography (EEG).

Technical developments have paved the way for the development of ultrasensitive analytical methods that allow for precise quantification of brain-specific proteins in blood samples. Plasma levels of amyloid β, specifically the Aβ42/40 ratio, are reduced in Alzheimer's disease (AD) and show concordance with brain amyloidosis assessed by PET, but the overlap with normal elderly may be too large for reliable use in clinical applications. Plasma phosphorylated tau (P-tau), especially a variant called P-tau217, is markedly increased in the early symptomatic stages of AD but remains normal in other neurodegenerative disorders. Total tau (T-tau) is measurable in blood and shows most promise as a biomarker for acute neuronal injury (e.g. acute traumatic or hypoxic brain injury), where T-tau shows a fast and dramatic increase but does not work well as an AD biomarker due to contributions to blood levels from peripheral tissues. Instead, a novel method for tau protein produced only in the CNS called brain-derived tau (BD-tau) shows promise as a biomarker for AD-type neurodegeneration. Neurofilament light (NFL) levels in blood correlate tightly with levels in CSF and reflect axonal injury irrespective of the underlying cause. Increased blood NFL concentration is found in several neurodegenerative disorders, including AD, but even more so in disorders such as motor neuron disease and frontotemporal dementia. Glial fibrillary acidic protein (GFAP) is expressed with activation of astrocytes, and is mildly increased in AD, but is also very high also in acute brain disorders. These blood tests show promise as tools to identify AD pathophysiology in the first assessment of patients with early cognitive symptoms, also in primary care, to guide clinical management and possible admission to the specialist clinic. A two-step model will result in a very high accuracy to either predict or exclude brain amyloidosis of the Alzheimer type.

During the past two decades, there have been many changes in automotive and medical technologies, road infrastructure, trauma systems, and demographic changes which may have influenced injury outcomes. The aim of this study was to examine injury trends among traffic casualties, specifically private car occupants, hospitalized in Level I Trauma Centers (TC).

Postconcussion syndrome (PCS) is one of the leading complications that may appear in patients after mild head trauma. Every day, thousands of people, regardless of age, gender, and race, are diagnosed in emergency departments due to head injuries. Traumatic Brain Injury (TBI) is a significant public health problem, impacting an estimated 1.5 million people in the United States and up to 69 million people worldwide each year, with 80% of these cases being mild. An analysis of the available research and a systematic review were conducted to search for a solution to predicting the occurrence of postconcussion syndrome. Particular biomarkers that can be examined upon admission to the emergency department after head injury were found as possible predictive factors of PCS development. Setting one unequivocal definition of PCS is still a challenge that causes inconsistent results. Neuron Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase-L1 (UCH-L1), Serum Protein 100 B (s100B), and tau protein are found to be the best predictors of PCS development. The presence of all mentioned biomarkers is confirmed in severe TBI. All mentioned biomarkers are used as predictors of PCS. A combined examination of NSE, GFAP, UCH-1, S100B, and tau protein should be performed to detect mTBI and predict the development of PCS.

One third of patients with epilepsy will continue to have uncontrolled seizures despite treatment with antiseizure medications (ASMs). There is therefore a need to develop novel ASMs. Brivaracetam (BRV) is an ASM that was developed in a major drug discovery program aimed at identifying selective, high-affinity synaptic vesicle protein 2A (SV2A) ligands, the target molecule of levetiracetam. BRV binds to SV2A with 15- to 30-fold higher affinity and greater selectivity than levetiracetam. BRV has broad-spectrum antiseizure activity in animal models of epilepsy, a favorable pharmacokinetic profile, few clinically relevant drug-drug interactions, and rapid brain penetration. BRV is available in oral and intravenous formulations and can be initiated at target dose without titration. Efficacy and safety of adjunctive BRV (50-200 mg/day) treatment of focal-onset seizures was demonstrated in three pivotal phase III trials (NCT00490035/NCT00464269/NCT01261325), including in patients who had previously failed levetiracetam. Efficacy and safety of adjunctive BRV were also demonstrated in adult Asian patients with focal-onset seizures (NCT03083665). In several open-label trials (NCT00150800/NCT00175916/NCT01339559), long-term safety and tolerability of adjunctive BRV was established, with efficacy maintained for up to 14 years, with high retention rates. Evidence from daily clinical practice highlights BRV effectiveness and tolerability in specific epilepsy patient populations with high unmet needs: the elderly (≥ 65 years of age), children (< 16 years of age), patients with cognitive impairment, patients with psychiatric comorbid conditions, and patients with acquired epilepsy of specific etiologies (post-stroke epilepsy/brain tumor related epilepsy/traumatic brain injury-related epilepsy). Here, we review the preclinical profile and clinical benefits of BRV from pivotal trials and recently published evidence from daily clinical practice.

The CRP/albumin ratio (CAR) is a mortality predictor in intensive care unit (ICU) patients. The aim of the current study was to investigate the ability of CAR to predict in-hospital mortality (IHM) in patients with isolated traumatic brain injury (iTBI). We performed a retrospective analysis including 200 patients with iTBI admitted to our neurosurgical intensive care unit (NICU) between September 2014 and December 2016. Serum biomarkers, demographic and radiological data, several ICU scores, and cardiopulmonary parameters were analyzed. The rate of IHM was 27.5% (55/200) and significantly associated with a higher AIS head score ( < 0.0001), a lower albumin level ( < 0.0001), and the necessity of a higher level of inspiratory oxygen fraction ( = 0.002). Furthermore, advanced age (odds ratio [OR] = 0.953, 95% confidence interval [CI] = 0.927-0.981, = 0.001), a lower GCS score (OR = 1.347, 95% CI = 1.203-1.509, < 0.0001), a higher level of lactate (OR = 0.506, 95% CI = 0.353-0.725, < 0.0001), a higher CAR (OR = 0.547, 95% CI = 0.316-0.945, = 0.031) and a higher norepinephrine application rate (OR = 0.000, 95% CI 0.000-0.090, = 0.016) were identified as independent predictors of IHM. ROC analysis showed an association between IHM and a CAR cut-off value of >0.38 (Youden index 0.073, sensitivity: 27.9, specificity: 64.8, = 0.044). We could identify a CAR > 0.38 as a new independent predictor for IHM in patients with iTBI.

Post-traumatic pituitary stalk transection syndrome (PSTS) is an extremely rare cause of combined pituitary hormone deficiency (CPHD), affecting approximately 9 per 100,000 cases of traumatic brain injury. In contrast, pituitary stalk interruption syndrome (PSIS) is also a rare cause of CPHD. Importantly, these conditions are often confused due to their similar names and resembling findings on magnetic resonance imaging (MRI). PSIS has been thought to be a prenatal developmental event resulting from a couple of genetic aberrations. In typical PSIS, anterior pituitary hormone deficiencies are restricted to growth hormone (GH) and gonadotropin during the pediatric age, gradually and generally progressing to panhypopituitarism in most cases. In contrast, global deficiencies of the anterior pituitary hormones in PSTS are temporally associated with trauma. To the best of our knowledge, no case reports of PSTS combined with acute traumatic spinal cord injury have been reported. A 34-year-old female was transferred to our hospital after jumping from the fourth building floor. She was diagnosed as an acute traumatic spinal cord injury and underwent the operation of elective posterior spinal fusion. On postoperative day 7, the blood tests revealed considerable hyperkalemia, hyponatremia and eosinophilia. Notably, menstruation stopped after falling from a height. Pituitary function tests revealed GH deficiency, hypogonadism, hypothyroidism and hypoadrenocorticism. MRI revealed loss of the pituitary stalk, whilst the hyperintense signal from distal axon of hypothalamus was still identified. Based on these findings, she was diagnosed as PSTS. Our case highlights endocrinological landscape of transection of the pituitary stalk by acute trauma.

Interrupted blood flow in the brain due to ischemic injuries such as ischemic stroke or traumatic brain injury results in irreversible brain damage, leading to cognitive impairment associated with inflammation, disruption of the blood-brain barrier (BBB), and cell death. Since the BBB only allows entry to a small class of drugs, many drugs used to treat ischemia in other tissues have failed in brain-related disorders. The administration of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) has shown promise in improving the functional recovery of the brain following cerebral ischemia by inducing blood vessel formation. To facilitate such a treatment approach, it is necessary to develop bioprocesses that can produce therapeutically relevant MSC-EVs in a reproducible and scalable manner. This study evaluated the feasibility of using stirred suspension bioreactors (SSBs) to scale-up the serum-free production of pro-angiogenic MSC-EVs under clinically relevant physioxic conditions. It was found that MSCs grown in SSBs generated EVs that stimulated angiogenesis in cerebral microvascular endothelial cells, supporting the use of SSBs to produce MSC-EVs for application in cerebral ischemia. These properties were impaired at higher cell confluency, outlining the importance of considering the time of harvest when developing bioprocesses to manufacture EV populations.

Traumatic brain injury (TBI) is the primary cause of child mortality and disability worldwide. It can result in severe complications that significantly impact children's quality of life, including post-traumatic epilepsy (PTE). An increasing number of studies suggest that TBI-induced oxidative stress and neuroinflammatory sequelae (especially inflammation in the hippocampus region) may lead to the development of PTE. Due to the blood-brain barrier (BBB), typical systemic pharmacological therapy for TBI cannot deliver berberine (BBR) to the targeted location in the early stages of the injury, although BBR has strong anti-inflammatory properties. To break through this limitation, we developed a microenvironment-responsive Gelatin methacrylate hydrogel (GM/PB) to deliver BBR for regulating neuroinflammatory reactions and removing ROS in the brain trauma microenvironment through poly(propylene sulfide) (PPS). In situ injection of the GM/PB hydrogel efficiently bypassed the BBB and was administered directly to the surface of brain tissue. In post-traumatic brain injury models, GM/PB has the potential to mitigate oxidative stress and neuroinflammatory responses, facilitate functional recovery, and lessen seizing. These findings could lead to a new treatment for brain injuries that minimizes complications and improves the quality of life. This article is protected by copyright. All rights reserved.

Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising human life and health. Activating transcription factor 4 (ATF4) participates in the regulation of multiple pathophysiological processes, including CNS disorders. Considering the widespread involvement of ATF4 in the pathological process of CNS disorders, the targeted regulation of ATF4 by plant-derived bioactive compounds (PDBCs) may become a viable strategy for the treatment of CNS disorders. However, the regulatory relationship between PDBCs and ATF4 remains incompletely understood. Here, we aimed to comprehensively review the studies on PDBCs targeting ATF4 to ameliorate CNS disorders, thereby offering novel directions and insights for the treatment of CNS disorders. A computerized search was conducted on PubMed, Embase, Web of Science, and Google Scholar databases to identify preclinical experiments related to PDBCs targeting ATF4 for the treatment of CNS disorders. The search timeframe was from the inception of the databases to December 2023. Two assessors conducted searches using the keywords "ATF4," "Central Nervous System," "Neurological," "Alzheimer's disease," "Parkinson's Disease," "Stroke," "Spinal Cord Injury," "Glioblastoma," "Traumatic Brain Injury," and "Spinal Cord Injury." Overall, 31 studies were included, encompassing assessments of 27 PDBCs. Combining results from in vivo and in vitro studies, we observed that these PDBCs, via ATF4 modulation, prevent the deposition of amyloid-like fibers such as Aβ, tau, and α-synuclein. They regulate ERS, reduce the release of inflammatory factors, restore mitochondrial membrane integrity to prevent oxidative stress, regulate synaptic plasticity, modulate autophagy, and engage anti-apoptotic mechanisms. Consequently, they exert neuroprotective effects in CNS disorders. Numerous PDBCs targeting ATF4 have shown potential in facilitating the restoration of CNS functionality, thereby presenting expansive prospects for the treatment of such disorders. However, future endeavors necessitate high-quality, large-scale, and comprehensive preclinical and clinical studies to further validate this therapeutic potential.

The purpose of this paper is to describe the implementation and outcomes of a unique traumatic brain injury (TBI) screening initiative serving the community, with a focus on underserved populations. Idaho's definition of underserved populations includes people living in rural/frontier areas, people experiencing homelessness or intimate partner violence, people with co-occurring disorders, and people with cultural and/or linguistically diverse backgrounds. The goals of screenings are to help participants gain awareness about the likelihood of having experienced a TBI, bridge the gap in TBI reporting, and provide needed support to underserved populations in a rural state.

Traumatic brain injury (TBI) is a leading cause of disability worldwide, with an estimated annual incidence of 27-69 million. TBI is a severe condition that can lead to high mortality rates and long-term cognitive, behavioral, and physical impairments in young adults. It is a significant public health concern due to the lack of effective treatments available. Quercetin, a natural flavonoid found in various fruits and vegetables, has demonstrated therapeutic potential with anti-inflammatory, antioxidant, and neuroprotective properties. Recently, some evidence has accentuated the ameliorating effects of quercetin on TBI. This review discusses quercetin's ability to reduce TBI-related damage by regulating many cellular and molecular pathways. Quercetin in vitro and in vivo studies exhibit promise in reducing inflammation, oxidative stress, apoptosis, and enhancing cognitive function post-TBI. Further clinical investigation into quercetin's therapeutic potential as a readily available adjuvant in the treatment of TBI is warranted in light of these findings. This review adds to our knowledge of quercetin's potential in treating TBI by clarifying its mechanisms of action.

The systematic review aimed to evaluate the effectiveness of nonpharmacological interventions (NPIs) for improving cognitive function among persons with traumatic brain injury.

Traumatic internal carotid artery (ICA) occlusion is a rare complication of skull base fractures, characterized by high mortality and disability rates, and poor prognosis. Therefore, timely discovery and correct management are crucial for saving the lives of such patients and improving their prognosis. This article retrospectively analyzed the imaging and clinical data of three patients, to explore the imaging characteristics and treatment strategies for carotid artery occlusion, combined with severe skull base fractures.

Mild traumatic brain injury (mTBI) is a significant health burden due to mTBI-related chronic debilitating cognitive and psychiatric morbidities. Recent evidence from our laboratory suggests a possible dysregulation within reward/motivational circuit function at the level of a subcortical structure, the lateral habenula (LHb), where we demonstrated a causal role for hyperactive LHb in mTBI-induced motivational deficits in self-care grooming behavior in young adult male mice when exposed to mTBI injury during late adolescence (at ~8 weeks old). Here we extended this observation by further characterizing neurobehavioral effects of this repetitive closed head injury model of mTBI in both young adult male and female mice on LHb excitability, corticotropin releasing factor (CRF) modulation of LHb activity, and behavioral responses of motivation to self-care behavior, and approach versus avoidance behavior in the presence of a social- or threat-related stimulus. We show that mTBI increases LHb spontaneous tonic activity in female mice similar to what we previously observed in male mice as well as promoting LHb neuronal hyperexcitability and hyperpolarization-induced LHb bursting in both male and female mice. Interestingly, mTBI only increases LHb intrinsic excitability in male mice coincident with higher levels of the hyperpolarization-activated cation currents (HCN/Ih) and reduces levels of the M-type potassium currents while potentiating M-currents without altering intrinsic excitability in LHb neurons of female mice. Since persistent dysregulation of brain CRF systems is suggested to contribute to chronic psychiatric morbidities and that LHb neurons are highly responsive to CRF, we then tested whether LHb CRF subsystem becomes engaged following mTBI. We found that inhibition of CRF receptor type 1 (CRFR1) within the LHb normalizes mTBI-induced enhancement of LHb tonic activity and hyperexcitability in both sexes, suggesting that an augmented intra-LHb CRF-CRFR1-mediated signaling contributes to the overall LHb hyperactivity following mTBI. Behaviorally, mTBI diminishes motivation for self-care grooming in female mice as in male mice. mTBI also alters defensive behaviors in the looming shadow task by shifting the innate defensive behaviors towards more passive action-locking rather than escape behaviors in response to an aerial threat in both male and female mice as well as prolonging the latency to escape responses in female mice. While, this model of mTBI reduces social preference in male mice, it induces higher social novelty seeking during the novel social encounters in both male and female mice. Overall, our study provides further translational validity for the use of this preclinical model of mTBI for investigation of mTBI-related reward circuit dysfunction and mood/motivation-related behavioral deficits in both sexes while uncovering a few sexually dimorphic neurobehavioral effects of this model that may differentially affect young males and females when exposed to this type of mTBI injury during late adolescence.

The outcomes of traumatic brain injury (TBI) exhibit variance contingent upon biological sex. Although female sex hormones exert neuroprotective effects, the administration of estrogen and progesterone has not yielded conclusive results. Hence, it is conceivable that additional mediators, distinct from female sex hormones, merit consideration due to their potential differential impact on TBI outcomes. Calcitonin gene-related peptide (CGRP) exhibits sexually dimorphic expression and demonstrates neuroprotective effects in acute brain injuries. In this study, we aimed to examine sex-based variations in TBI structural and functional outcomes with respect to CGRP expression.

The lectin pathway (LP) of complement mediates inflammatory processes linked to tissue damage and loss of function following traumatic brain injury (TBI). LP activation triggers a cascade of proteolytic events initiated by LP specific enzymes called MASPs (for Mannan-binding lectin Associated Serine Proteases). Elevated serum and brain levels of MASP-2, the effector enzyme of the LP, were previously reported to be associated with the severity of tissue injury and poor outcomes in patients with TBI. To evaluate the therapeutic potential of LP inhibition in TBI, we first conducted a pilot study testing the effect of an inhibitory MASP-2 antibody (α-MASP-2), administered systemically at 4 and 24 h post-TBI in a mouse model of controlled cortical impact (CCI). Treatment with α-MASP-2 reduced sensorimotor and cognitive deficits for up to 5 weeks post-TBI. As previous studies by others postulated a critical role of MASP-1 in LP activation, we conducted an additional study that also assessed treatment with an inhibitory MASP-1 antibody (α-MASP-1). A total of 78 mice were treated intraperitoneally with either α-MASP-2, or α-MASP-1, or an isotype control antibody 4 h and 24 h after TBI or sham injury. An amelioration of the cognitive deficits assessed by Barnes Maze, prespecified as the primary study endpoint, was exclusively observed in the α-MASP-2-treated group. The behavioral data were paralleled by a reduction of the lesion size when evaluated histologically and by reduced systemic LP activity. Our data suggest that inhibition of the LP effector enzyme MASP-2 is a promising treatment strategy to limit neurological deficits and tissue loss following TBI. Our work has translational value because a MASP-2 antibody has already completed multiple late-stage clinical trials in other indications and we used a clinically relevant treatment protocol testing the therapeutic mechanism of MASP-2 inhibition in TBI.

To analyze the impact of positive end-expiratory pressure (PEEP) changes on intracranial pressure (ICP) dynamics in patients with acute brain injury (ABI).

The purpose of this study was to interrogate brain iron accumulation in participants with acute post-traumatic headache (PTH) due to mild traumatic brain injury (mTBI), and to determine if functional connectivity is affected in areas with iron accumulation. We aimed to examine the correlations between iron accumulation and headache frequency, post-concussion symptom severity, number of mTBIs, and time since most recent TBI.

Traumatic brain injury (TBI) is a complex pathophysiological process that results in a variety of neurotransmitter, behavioral, and cognitive deficits. The locus coeruleus-norepinephrine (LC-NE) system is a critical regulator of arousal levels and higher executive processes affected by TBI including attention, working memory, and decision making. LC-NE axon injury and impaired signaling within the prefrontal cortex (PFC) is a potential contributor to the neuropsychiatric symptoms after single, moderate to severe TBI. The majority of TBIs are mild, yet long-term cognitive deficits and increased susceptibility for further injury can accumulate after each repetitive mild TBI. As a potential treatment for restoring cognitive function and daytime sleepiness after injury psychostimulants, including methylphenidate (MPH) that increase levels of NE within the PFC, are being prescribed "off-label". The impact of mild and repetitive mild TBI on the LC-NE system remains limited. Therefore, we determined the extent of LC-NE and arousal dysfunction and response to therapeutic doses of MPH in rats following experimentally induced single and repetitive mild TBI. Microdialysis measures of basal NE efflux from the medial PFC and arousal measures were significantly lower after repetitive mild TBI. Females showed higher baseline PFC-NE efflux than males following single and repetitive mild TBI. In response to MPH challenge, males exhibited a blunted PFC-NE response and persistent arousal levels following repetitive mild TBI. These results provide critical insight into the role of catecholamine system dysfunction associated with cognitive deficits following repeated injury, outcome differences between sex/gender, and lack of success of MPH as an adjunctive therapy to improve cognitive function following injury.

Post-traumatic seizures (PTSs) contribute to morbidity after traumatic brain injury (TBI). Early PTS are rare in combat casualties sustaining TBI, but the prevalence of late PTS is poorly described. We sought to define the prevalence and risk factors of late PTS in combat casualties with computed tomography evidence of TBI.

We aim to evaluate the association of early versus late venous thromboembolism (VTE) prophylaxis on in-hospital mortality among patients with severe blunt isolated traumatic brain injuries.

In ischaemic stroke, a large reduction in blood supply can lead to the breakdown of the blood-brain barrier and to cerebral oedema after reperfusion therapy. The resulting fluid accumulation in the brain may contribute to a significant rise in intracranial pressure (ICP) and tissue deformation. Changes in the level of ICP are essential for clinical decision-making and therapeutic strategies. However, the measurement of ICP is constrained by clinical techniques and obtaining the exact values of the ICP has proven challenging. In this study, we propose the first computational model for the simulation of cerebral oedema following acute ischaemic stroke for the investigation of ICP and midline shift (MLS) relationship. The model consists of three components for the simulation of healthy blood flow, occluded blood flow and oedema, respectively. The healthy and occluded blood flow components are utilized to obtain oedema core geometry and then imported into the oedema model for the simulation of oedema growth. The simulation results of the model are compared with clinical data from 97 traumatic brain injury patients for the validation of major model parameters. Midline shift has been widely used for the diagnosis, clinical decision-making, and prognosis of oedema patients. Therefore, we focus on quantifying the relationship between ICP and midline shift (MLS) and identify the factors that can affect the ICP-MLS relationship. Three major factors are investigated, including the brain geometry, blood-brain barrier damage severity and the types of oedema (including rare types of oedema). Meanwhile, the two major types (stress and tension/compression) of mechanical brain damage are also presented and the differences in the stress, tension, and compression between the intraparenchymal and periventricular regions are discussed. This work helps to predict ICP precisely and therefore provides improved clinical guidance for the treatment of brain oedema.

This investigation examined the potential of ginsenoside Rg3 in addressing traumatic brain injury (TBI). A TBI mouse model underwent treatment with ginsenoside Rg3 and nicotinamide (NAM). Neurological and motor functions were assessed using modified neurological severity score and rotarod tests. Brain water content in mice was detected. Primary mouse microglia were exposed to lipopolysaccharide (LPS), ginsenoside Rg3, and NAM. Nissl and immunofluorescence staining were utilized to investigate hippocampal damage, and localization of P65, Iba1 and INOS in microglia. Hippocampal neurons were grown in a culture medium derived from microglia. CCK-8 and TUNEL assays were employed to evaluate the viability and apoptosis of hippocampal neurons. Proinflammatory factors and proteins were tested using ELISA, western blot and immunofluorescence staining. As a result, ginsenoside Rg3 enhanced neurological and motor functions in mice post-TBI, reduced brain water content, alleviated hippocampal neuronal neuroinflammation and damage, activated SIRT1, and deactivated the NF-kB pathway. In LPS-stimulated microglia, ginsenoside Rg3 diminished inflammation, activated SIRT1, deactivated the NF-kB pathway, and facilitated nuclear localization of P65 and co-localization of Iba1 and INOS. The effects of ginsenoside Rg3 were countered by NAM in both TBI mice and LPS-stimulated microglia. Hippocampal neurons cultured in a medium containing LPS, ginsenoside Rg3, and NAM-treated microglia showed improved viability and reduced apoptosis compared to those cultured in a medium with LPS and ginsenoside Rg3-treated microglia alone. Ginsenoside Rg3 was effective in reducing neuroinflammation and damage in hippocampal neurons following TBI by modulating the SIRT1/NF-kB pathway, suggesting its potential as a therapeutic agent for TBI.

Intracranial pressure (ICP) monitoring plays a key role in patients with traumatic brain injury (TBI), however, cerebral hypoxia can occur without intracranial hypertension. Aiming to improve neuroprotection in these patients, a possible alternative is the association of Brain Tissue Oxygen Pressure (PbtO2) monitoring, used to detect PbtO2 tension.

The intricate regulatory relationship between mitochondrial dysfunction, apoptosis, and immune cells remains largely elusive following traumatic brain injury (TBI).

In preclinical traumatic brain injury (TBI) research, the animal model should be selected based on the research question and outcome measures of interest. Direct side by side comparisons of different injury models are essential for informing such decisions. Here, we used immunohistochemistry to compare the outcomes from two common models of TBI, lateral fluid percussion (LFP) and repeated mild weight drop (rmWD) in adult female and male Wistar rats. Specifically, we measured the effects of LFP and rmWD on markers of cerebrovascular and tight junction disruption, neuroinflammation, mature neurons, and perineuronal nets in the cortical site of injury, cortex adjacent to injury, dentate gyrus, and the CA2/3 area of the hippocampus. Animals were randomized into LFP or rmWD groups. On day 1, the LFP group received a craniotomy and on day 4, injury (or sham procedure; randomly assigned). The rmWD animals underwent either injury or isoflurane-only (randomly assigned) on each of those 4 days. Seven days after injury, brains were harvested for analysis. Overall, our observations revealed that the most significant disruptions were evident in response to LFP, followed by craniotomy-only, while rmWD animals showed the least residual changes compared to isoflurane-only controls, supporting consideration of rmWD as a mild injury. LFP led to longer-lasting disruptions, perhaps more representative of moderate TBI. We also report that craniotomy and LFP produced greater disruptions in females relative to males. These findings will assist the field in the selection of animal models based on target severity of post-injury outcomes, and support the inclusion of both sexes and appropriate control groups.

Resting-state electroencephalography (rsEEG) is usually obtained to assess seizures in comatose patients with traumatic brain injury (TBI). We aim to investigate rsEEG measures and their prediction of early recovery of consciousness in patients with TBI.

To describe a dog with suspected cerebral salt wasting syndrome (CSWS) secondary to traumatic brain injury (TBI).

Background Sports concussion (SC) management guidelines have recently been updated. A key focus is the emphasis on rest (immediately postinjury) followed by gradual resumption of activity (active recovery). This study aimed to explore community views on SC management and compared these with the guidelines. Methods A total of 157 volunteers completed an online SC survey, including listing three pieces of advice for a concussed person immediately postinjury, and after 2weeks (subacute). Quantitative data were statistically compared, and qualitative data underwent content analysis. Results Almost all participants offered different immediate versus subacute advice; however, rest featured highly at both timepoints. Commonly expressed themes, consistent with guidelines were immediate rest; safety and reinjury prevention; and symptom monitoring. Two themes were identified in the community advice with limited emphasis in the guidelines: general health advice and psychological and social support. Expert clinical assessment was not always identified in community advice. Conclusion Community members hold some views that align with expert advice for SC, particularly the importance of immediate postinjury rest. However, there is scope to grow public awareness of some recommended practices, including expert clinical assessment following injury and when to engage in active recovery.

Traumatic brain injury (TBI), particularly mild TBI (mTBI), is a significant health concern for U.S. active duty service members (ADSMs), with potential implications for psychiatric outcomes including PTSD. Despite recognizing this association, the prevalence of PTSD among ADSMs with mTBI remains unclear.

Traumatic brain injury (TBI) is an acute injury that is understudied in civilian cohorts, especially among women, as TBI has historically been considered to be largely a condition of athletes and military service people. Both the Centres for Disease Control and Prevention (CDC) and Department of Defense (DOD)/Veterans Affairs (VA) have developed case definitions to identify patients with TBI from medical records; however, their definitions differ. We sought to re-examine these definitions to construct an expansive and more inclusive definition among a cohort of women with TBI.

Every year, thousands of people in Germany succumb to severe injuries. But what causes the death of these patients? In addition to the trauma, pre-traumatic health status, age, and other influencing factors play a role in the outcome after trauma. This study aims to answer the question of what causes the death of a severely injured patient.For this publication, in addition to previously published results, we examined current data from patients in German hospitals from the years 2015-2022 (8 years) documented in the TraumaRegister DGU®. The feature "Presumed Cause of Death", introduced in 2015, was considered. Patients transferred out early (< 48 h) as well as patients with minor injuries were excluded from this analysis.The number of fatalities decreases over time and does not correspond to a traditionally postulated tri-modal mortality distribution. Instead, over time, the distribution of causes of death shows significant variation. In over half of the cases (54%), traumatic brain injury (TBI) was the presumed cause of death, followed by organ failure (24%) and haemorrhage (9%). TBI dominates, especially in the first week, haemorrhage in the first 24 h, and organ failure as a cause steadily increases over time.In summary, it can be observed that the risk of death due to trauma-related consequences is highest in the first minutes, hours, and days, decreasing steadily over time. Particularly, the extent of injuries, head injuries, and significant blood loss are early risk factors.

Mitochondrial dysfunction and oxidative stress are important mechanisms for secondary injury after traumatic brain injury (TBI), which result in progressive pathophysiological exacerbation. Although the Fibronectin type III domain-containing 5 (FNDC5) was reported to repress oxidative stress by retaining mitochondrial biogenesis and dynamics, its possible role in the secondary injury after TBI remain obscure. In present study, we observed that the level of serum irisin (the cleavage product of FNDC5) significantly correlated with the neurological outcomes of TBI patients. Knockout of FNDC5 increased the lesion volume and exacerbated apoptosis and neurological deficits after TBI in mice, while FNDC5 overexpression yielded a neuroprotective effect. Moreover, FNDC5 deficiency disrupted mitochondrial dynamics and function. Activation of Sirtuin 3 (SIRT3) alleviated FNDC5 deficiency-induced disruption of mitochondrial dynamics and bioenergetics. In neuron-specific SIRT3 knockout mice, FNDC5 failed to attenuate TBI-induced mitochondrial damage and brain injuries. Mechanically, FNDC5 deficiency led to reduced SIRT3 expression via enhanced ubiquitin degradation of transcription factor Nuclear factor erythroid 2-related factor 2 (NRF2), which contributed to the hyperacetylation and inactivation of key regulatory proteins of mitochondrial dynamics and function, including OPA1 and SOD2. Finally, engineered RVG29-conjugated nanoparticles were generated to selectively and efficiently deliver irisin to the brain of mice, which yielded a satisfactory curative effect against TBI. In conclusion, FNDC5/irisin exerts a protective role against acute brain injury by promoting SIRT3-dependent mitochondrial quality control and thus represents a potential target for neuroprotection after TBI.

Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide, particularly among the elderly, yet our mechanistic understanding of what renders the post-traumatic brain vulnerable to poor outcomes, and susceptible to neurological disease, is incomplete. It is well established that dysregulated and sustained immune responses elicit negative consequences after TBI; however, our understanding of the neuroimmune interface that facilitates crosstalk between central and peripheral immune reservoirs is in its infancy. The meninges serve as the interface between the brain and the immune system, facilitating important bi-directional roles in both healthy and disease settings. It has been previously shown that disruption of this system exacerbates neuroinflammation in age-related neurodegenerative disorders such as Alzheimer's disease; however, we have an incomplete understanding of how the meningeal compartment influences immune responses after TBI. In this manuscript, we will offer a detailed overview of the holistic nature of neuroinflammatory responses in TBI, including hallmark features observed across clinical and animal models. We will highlight the structure and function of the meningeal lymphatic system, including its role in immuno-surveillance and immune responses within the meninges and the brain. We will provide a comprehensive update on our current knowledge of meningeal-derived responses across the spectrum of TBI, and identify new avenues for neuroimmune modulation within the neurotrauma field.

This commentary seeks to evaluate existing knowledge about the relationship between brain injury (BI) and overdose (OD), to unify distant bodies of literature, and to enhance prevention and treatment for opioid OD among individuals with BI.

Background This study investigates the impact of New York's relaxed alcohol consumption policies during the coronavirus disease (COVID-19) pandemic on alcohol-related traumatic brain injuries (TBIs) among patients admitted to a Level 1 trauma center in Queens. Given the limited research available, this study critically explores the link between public health policies and trauma care. It aims to address a significant gap in the literature and highlight the implications of alcohol regulations during global health emergencies. Methodology A retrospective analysis was conducted among trauma patients from 2019 to 2021. The study period was divided into the following three periods: pre-lockdown (March 7, 2019, to July 31, 2019), lockdown (March 7, 2020, to July 31, 2020), and post-lockdown (March 7, 2021, to July 31, 2021). Data on demographics, injury severity, comorbidities, and outcomes were collected. The study focused on assessing the correlation between New York's alcohol policies and alcohol-related TBI admissions during these periods. Results A total of 1,074 admissions were analyzed. The study found no significant changes in alcohol-positive patients over the full calendar years of 2019, 2020, and 2021 (42.65%, 38.91%, and 31.16% respectively; p = 0.08711). Specifically, during the lockdown period, rates of alcohol-positive TBI patients remained unchanged, despite the relaxed alcohol policies. There was a decrease in alcohol-related TBI admissions in 2021 compared to 2020 during the lockdown period. Conclusions Our study concludes that New York's specific alcohol policies during the COVID-19 pandemic were not correlated with an increase in alcohol-related TBI admissions. Despite the relaxation of alcohol consumption laws, there was no increase in alcohol positivity among TBI patients. The findings suggest a complex relationship between public policies, alcohol use, and trauma during pandemic conditions, indicating that factors other than policy relaxation might influence alcohol-related trauma incidences.

The incidence and prevalence of concussion, a type of mild traumatic brain injury (mTBI), have steadily increased among athletes, both students and professionals, across a wide variety of sports, including, but not limited to, swimming, tennis, football, and boxing. Recent data have demonstrated that sports are one of the leading causes of concussions among student athletes. While the exact mechanism of concussion onset has yet to be fully elucidated, data suggest that the pathophysiology involves rotational acceleration and deceleration of the brain, leading to axon tearing and disturbance in the metabolic cascade of glucose. Concussive events can have debilitating effects on an athlete, including chronic traumatic encephalopathy (gradual degeneration of brain tissue) that is related to personality changes, emotional disorders, and even dementia. Common symptoms associated with concussion include dizziness, nausea, vomiting, and headaches. The physical assessment consists of a combination of tools involving the mental status examination, vital signs, cervical spine exam, eye exam, and neurological testing. The use of osteopathic manipulative medicine (OMM), pharmacotherapy, hyperbaric oxygen therapy (HBOT), aerobic exercise, balance, and/or vestibular therapy are many common treatment approaches for concussion and post-concussion sequelae. This literature review aims to provide insight into concussions, the current treatment options available, and the new developments in concussions per the Amsterdam 2022 International Consensus Statement on Concussion in Sport published in 2023.

To evaluate the effect of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) on regional cerebral oxygen saturation (rScO) during induction of general anesthesia in patients undergoing traumatic brain injury (TBI) emergency surgery.

Meningitis is the inflammation of meninges either septic or aseptic depending on the source of infection. Typical signs and symptoms of meningitis in children include fever, headache, neck stiffness, nuchal rigidity represented by positive Kernig and Brudzinski signs, photophobia, nausea, vomiting, confusion, lethargy, and irritability. Bacterial meningitis is commonly caused by  in children over the age of three months. Although there has been a decline in infections due to the introduction of the pneumococcal conjugate and pneumococcal polysaccharide vaccines, there are still reported cases of invasive pneumococcal infections mostly with non-vaccine serotypes. We report a fully immunized six-year-old male patient with a presentation of classic meningitis signs and symptoms who developed rapid progression of disease including sudden and dramatic change in physical exam and subsequent respiratory depression within 12 hours of admission. Our patient had a history of extensive traumatic facial bone fractures six months prior. Our case demonstrates a unique presentation of rapidly progressing pneumococcal meningitis due to a suspected complication of septic thrombophlebitis and subsequent brain herniation in a fully immunized patient six months after a severe traumatic facial injury.

Virtual reality (VR)-based interventions to improve balance and mobility are gaining increasing traction across patient populations. VR-based interventions are believed to be more enjoyable and engaging for patients with traumatic brain injury. This scoping review aims to summarize existing studies from the literature that used VR to improve balance and mobility and determine the gap in VR-based balance literature specific to individuals with traumatic brain injury.

Traumatic brain injury (TBI) stands as a prominent global cause of disability, with motor deficits being a common consequence. Despite its widespread impact, the precise pathological mechanisms underlying motor deficits after TBI remain elusive In this study, hindlimb postural asymmetry (HL-PA) development in rats subjected to focal TBI was investigated to explore the potential roles of collagen IV and laminin within the extracellular matrix (ECM) of selected hindlimb muscles in the emergence of motor deficits following TBI. A focal TBI was induced by ablating the left sensorimotor cortex in rats and motor deficits were assessed by measuring HL-PA. The expression of laminin and collagen IV in eight selected muscles on each side of the hindlimbs from both TBI- and sham-operated rats were studied using immunohistochemistry and semi-quantitatively analyzed. The results indicated that the TBI rats exhibited HL-PA, characterized by flexion of the contralateral (right) hindlimb. In the sham-operated rats, the immunoreactive components of laminin and collagen IV were evenly and smoothly distributed along the border of the muscle fibers in all the investigated muscles. In contrast, in the TBI rats, the pattern was broken into aggregated, granule-like, immunoreactive components. Such a labeling pattern was detected in all the investigated muscles both from the contra- and ipsilateral sides of the TBI rats. However, in TBI rats, most of the muscles from the contralateral hindlimb showed a significantly increased expression of these two proteins in comparison with those from the ipsilateral hindlimb. In comparison to sham-operated rats, there was a significant increase in laminin and collagen IV expression in various contralateral hindlimb muscles in the TBI rats. These findings suggest potential implications of laminin and collagen IV in the development of motor deficits following a focal TBI.

Children aged 0-4 years have the highest rate of emergency department (ED) visits for traumatic brain injury (TBI); falls are the leading cause. Infants younger than 2 years are more likely to sustain a fractured skull after a fall.

Research studies have presented an unappreciated relationship between intimate partner violence (IPV) survivors and symptoms of traumatic brain injuries (TBI). Within these IPV survivors, resulting TBIs are not always identified during emergency room visits. This demonstrates a need for a prescreening tool that identifies IPV survivors who should receive TBI screening. We present a model that measures similarities to clinical reports for confirmed TBI cases to identify whether a patient should be screened for TBI. This is done through an ensemble of three supervised learning classifiers which work in two distinct feature spaces. Individual classifiers are trained on clinical reports and then used to create an ensemble that needs only one positive label to indicate a patient should be screened for TBI.

Neuro-monitoring is widely employed for the evaluation of intubated patients in the intensive care unit with stroke, severe head trauma, subarachnoid hemorrhage and/or hepatic encephalopathy. The present study reports the case of a patient with acute intracranial hemorrhage following the insertion of neuromonitoring catheters, which required surgical management. The patient was a 14-year-old male who sustained a severe traumatic brain injury and underwent a right-sided hemicraniectomy. During the installation of the neuromonitoring catheters, an acute hemorrhage was noted with a rapidly elevating intracranial pressure. A craniotomy was performed to identify and coagulate the injured cortical vessel. As demonstrated herein, the thorough evaluation of the clotting profile of the patient, a meticulous surgical technique and obtaining a post-insertion computed tomography scan may minimize the risk of any neuromonitoring-associated hemorrhagic complications.

Knowledge about the mechanisms underlying the fluid flow in the brain and spinal cord is essential for discovering the mechanisms implicated in the pathophysiology of central nervous system diseases. During recent years, research has highlighted the complexity of the fluid flow movement in the brain through a glymphatic system and a lymphatic network. Less is known about these pathways in the spinal cord. An important aspect of fluid flow movement through the glymphatic pathway is the role of water channels, especially aquaporin 1 and 4. This review provides an overview of the role of these aquaporins in brain and spinal cord, and give a short introduction to the fluid flow in brain and spinal cord during in the healthy brain and spinal cord as well as during traumatic brain and spinal cord injury. Finally, this review gives an overview of the current knowledge about the role of aquaporins in traumatic brain and spinal cord injury, highlighting some of the complexities and knowledge gaps in the field.

Predictive scales have been used to prognosticate long-term outcomes of traumatic brain injury (TBI), but gaps remain in predicting mortality using initial trauma resuscitation data. We sought to evaluate the association of clinical variables collected during the initial resuscitation of intubated pediatric severe patients with TBI with in-hospital mortality.

Benign paroxysmal positional vertigo (BPPV) affects approximately half of acute, moderate-severe traumatic brain injury (TBI) patients. To date, there have been no rigorous studies of BPPV assessment or treatment in this cohort. We aimed to determine the safety, practicability, and efficacy of therapist-led BPPV management in acute TBI and the feasibility of a larger effectiveness trial.

Traumatic brain injury (TBI) is a leading cause of morbidity, disability, and mortality worldwide. Motor and cognitive deficits and emotional disturbances are long-term consequences of TBI. A lack of effective treatment for TBI-induced neural damage, functional impairments, and cognitive deficits makes it challenging in the recovery following TBI. One of the reasons may be the lack of knowledge underlying the complex pathophysiology of TBI and the regulatory factors involved in the cellular and molecular mechanisms of inflammation, neural regeneration, and injury repair. These mechanisms involve a change in the expression of various proteins encoded by genes whose expression is regulated by transcription factors (TFs) at the transcriptional level and microRNA (miRs) at the mRNA level. In this pilot study, we performed the RNA sequencing of injured tissues and non-injured tissues from the brain of Yucatan miniswine and analyzed the sequencing data for differentially expressed genes (DEGs) and the TFs and miRs regulating the expression of DEGs using in-silico analysis. We also compared the effect of the electromagnetic field (EMF) applied to the injured miniswine on the expression profile of various DEGs. The results of this pilot study revealed a few DEGs that were significantly upregulated in the injured brain tissue and the EMF stimulation showed effect on their expression profile.

Extracellular cold-inducible RNA-binding protein (eCIRP) plays a vital role in the inflammatory response during cerebral ischaemia. However, the potential role and regulatory mechanism of eCIRP in traumatic brain injury (TBI) remain unclear. Here, we explored the effect of eCIRP on the development of TBI using a neural-specific CIRP knockout (KO) mouse model to determine the contribution of eCIRP to TBI-induced neuronal injury and to discover novel therapeutic targets for TBI.

The objective was to investigate the effectiveness of a person-centred active rehabilitation programme on symptoms associated with suspected Chronic Traumatic Encephalopathy (CTE). This was accomplished by (1) assessing the effect that a person-centred active rehabilitation programme had on participant symptoms, and (2) exploring how temporal contextual factors affected the participants' experience with, and perceived effectiveness of, the active rehabilitation programme.

This study evaluates the use of the crosswalk between the PTSD Checklist-Civilian (PCL-C) and PTSD Checklist for DSM-5 (PCL-5) designed by Moshier et al. (2019) in a sample of service members and veterans (SM/V; N = 298) who had sustained a traumatic brain injury (TBI) and were receiving inpatient rehabilitation. The PCL-C and PCL-5 were completed at the same time. Predicted PCL-5 scores for the sample were obtained according to the crosswalk developed by Moshier et al. We used three measures of agreement: intraclass correlation coefficient (ICC), mean difference between predicted and observed scores, and Cohen's κ to determine the performance of the crosswalk in this sample. Subgroups relevant to those who have sustained a TBI, such as TBI severity, were also examined. There was strong agreement between the predicted and observed PCL-5 scores (ICC = .95). The overall mean difference between predicted and observed PCL-5 scores was 0.07 and not statistically significant (SD = 8.29, p = .89). Significant mean differences between predicted and observed PCL-5 scores calculated between subgroups were seen in Black participants (MD = -4.09, SD = 8.41, p = .01) and those in the Year 5 follow-up group (MD = 1.77, SD = 7.14, p = .03). Cohen's κ across subgroups had a mean of κ = 0.76 (.57-1.0), suggesting that there was moderate to almost perfect diagnostic agreement. Our results suggest the crosswalk created by Moshier et al. can be applied to SM/V who have suffered a TBI. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The blood-brain barrier (BBB) is a dynamic interface that regulates the exchange of molecules and cells between the brain parenchyma and the peripheral blood. The BBB is mainly composed of endothelial cells, astrocytes and pericytes. The integrity of this structure is essential for maintaining brain and spinal cord homeostasis and protection from injury or disease. However, in various neurological disorders, such as traumatic brain injury, Alzheimer's disease, and multiple sclerosis, the BBB can become compromised thus allowing passage of molecules and cells in and out of the central nervous system parenchyma. These agents, however, can serve as biomarkers of BBB permeability and neuronal damage, and provide valuable information for diagnosis, prognosis and treatment. Herein, we provide an overview of the BBB and changes due to aging, and summarize current knowledge on biomarkers of BBB disruption and neurodegeneration, including permeability, cellular, molecular and imaging biomarkers. We also discuss the challenges and opportunities for developing a biomarker toolkit that can reliably assess the BBB in physiologic and pathophysiologic states.

Trauma primarily affects the economically active population, causing social and economic impact. The non-operative management of solid organ injuries aims to preserve organ function, reducing the morbidity and mortality associated with surgical interventions. The aim of study was to demonstrate the epidemiological profile of patients undergoing non-operative management in a trauma hospital and to evaluate factors associated with mortality in these patients.

Traumatic brain injury (TBI) negatively impacts social communication in part due to social cognitive difficulties, which may include reduced mental state term (MST) use in some discourse genres. As social cognitive difficulties can negatively impact relationships, employment, and meaningful everyday activities, assessing and treating these difficulties post-TBI is crucial. To address knowledge gaps, the present study examined MST use in the narrative retells of adults with and without severe TBI to compare between-group performance, evaluate changes over the first two years post-TBI, and investigate the impact of participant and injury-related variables.

Traumatic brain injury (TBI), a leading cause of high morbidity and mortality, represents a significant global public health challenge. Currently, no effective treatment for TBI exists. Curcumin, an active compound extracted from the root of , has demonstrated neuroprotective properties both and . Notably, it has shown potential in reducing oxidative stress and inflammation and enhancing redox balance. This paper conducts a systematic review and meta-analysis to explore curcumin's role in TBI animal models extensively. The findings offer valuable insights for future human clinical trials evaluating curcumin as a therapeutic supplement or nutraceutical in TBI management.