- Whole-brain immediate-early gene mapping identified the paraventricular thalamus as persistently hyperactive and central in chronic cerebral hypoperfusion.
- Chemogenetic PVT inhibition early reduced neuronal damage in mPFC, hippocampus and white matter, and improved cognition and sleep continuity.
- Early thalamic-hypothalamic hyperactivation precedes delayed cortical deactivation, suggesting early hub suppression may limit network-wide pathology in CCH.
iScience. 2026 Aug 5;29(8):117108. doi: 10.1016/j.isci.2026.117108. eCollection 2026 Aug 21.
ABSTRACT
Chronic cerebral hypoperfusion (CCH) is a key pathophysiological substrate of vascular cognitive impairment, and the reorganization of neuronal activity across disease progression underlies network dysfunction and intervention strategy. Using immediate-early gene imaging with whole-brain mapping, we characterized spatiotemporal activation patterns in a bilateral common carotid artery stenosis mouse model at early (day 7) and chronic (day 40) stages across 225 brain regions. Weighted gene co-expression network analysis identified the paraventricular thalamus (PVT) as a persistently hyperactive and central region, with early thalamic-hypothalamic hyperactivation giving way to delayed cortical deactivation at chronic stages. Chemogenetic inhibition of PVT during the early post-ischemic phase attenuated neuronal damage in medial prefrontal cortex, hippocampus, and white matter, and improved cognitive performance and sleep continuity. These findings implicate PVT hyperactivation as a disease-associated node contributing to network-wide pathology in CCH, and suggest that early suppression of a central hub may help limit distributed injury.
PMID:42602569 | PMC:PMC13474078 | DOI:10.1016/j.isci.2026.117108
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