INVESTIGATING THE CEREBRAL VASCULAR INTEGRITY IN A CHRONIC CEREBRAL HYPOPERFUSION MOUSE MODEL OF VASCULAR DEMENTIA - FROM PATHOPHYSIOLOGY TO TREATMENT

Abstract

Chronic cerebral hypoperfusion (CCH) has been well-established as a major underlying cause for upregulation of molecular and cellular pathological mechanisms, thus is invariantly a prominent feature of neurodegeneration in Vascular Dementia (VaD). Experimentally inducing CCH via bilateral common carotid artery stenosis (BCAS) in mice has demonstrated development of pathological features that mimic human patients. An additional layer to the project is to explore possible treatment option, specifically, Intermittent fasting (IF). Here we investigated whether IF (16h fasting per day) alleviates neurovascular damages in mice brain. Comprehensive analysis revealed that IF reduced neuronal and vascular pathologies by reducing microbleeds, blood-brain-barrier breakdown, severity of white matter lesions, and hippocampal cell death. Mechanistically, IF decreased activation of metalloproteinase and oxidative stress markers following CCH. In conclusion, IF preserves vascular and neuronal integrities in CCH-induced mice, therefore suggesting IF as an effective means of preventing the onset or suppressing the development pathologies in VaD.