- Edaravone and flurbiprofen monotherapies improved social interaction, reduced anxiety and memory deficits, lowering IL-6, TNF-α and oxidative stress while restoring GPX and SOD.
- Combination therapy produced no additive benefit over monotherapy, indicating either drug alone achieves maximal behavioural and hippocampal rescue in the VPA autism model.
- Findings reveal a convergent therapeutic ceiling, challenging combinatorial polypharmacy and informing targeted strategies against overlapping oxidative and inflammatory pathways in ASD.
IBRO Neurosci Rep. 2026 Jul 27;21:342-351. doi: 10.1016/j.ibneur.2026.07.017. eCollection 2026 Dec.
ABSTRACT
BACKGROUND AND OBJECTIVES: Autism Spectrum Disorder (ASD) presents significant therapeutic challenges, with growing evidence implicating neuroinflammation and oxidative stress in its pathophysiology. This study aimed to investigate the protective effects of edaravone and flurbiprofen, administered alone and in combination, in a valproic acid (VPA)-induced autism model in male rats.
MATERIALS AND METHODS: An autism model was established through prenatal VPA exposure. Social behavior, anxiety, and memory were assessed using a battery of standardized behavioral tests. Pro-inflammatory and oxidative stress markers were evaluated via ELISA, and hippocampal neuronal density was assessed by Nissl staining.
RESULTS: All treatment groups (edaravone, flurbiprofen, and their combination) showed significant improvements in autism-related behaviors, including enhanced social interaction, reduced memory deficits, and decreased anxiety. The treatments lowered pro-inflammatory cytokines (IL-6, TNF-α) and MDA levels, while restoring the activity of antioxidant enzymes GPX and SOD.
CONCLUSIONS: Edaravone and flurbiprofen effectively improved autism-like behaviors by targeting shared pathways of oxidative stress and neuroinflammation. However, the combination therapy offered no additive benefits over monotherapy. This finding suggests that monotherapy with either drug is sufficient to achieve maximal therapeutic effects, a point with significant implications for future treatment strategies in ASD.
SIGNIFICANCE STATEMENT: This study advances neurodevelopmental neuroscience by demonstrating that independently targeting oxidative stress or neuroinflammation achieves maximal behavioral and hippocampal rescue in an autism model, revealing a convergent therapeutic ceiling that challenges combinatorial polypharmacy and refines our understanding of how overlapping pathological pathways govern neural circuit dysfunction and functional recovery.
PMID:42571262 | PMC:PMC13451920 | DOI:10.1016/j.ibneur.2026.07.017
Share Evidence Blueprint
Save to Google Notes
Search Google Scholar
Save as PDF
⭐ My Revision List
