Effects of intermittent fasting on the cerebrovascular pathology and cognitive impairment in a mouse model of subcortical vascular dementia

Abstract

Intermittent fasting (IF) is found to exhibit neuroprotection across various insults, but whether IF treatment after an established ischemic or hypoperfusion condition can prevent the long-term detrimental effects remains a question. Here, I investigated the effects of IF intervention on cognitive impairments and cerebrovascular pathologies manifested by the chronic cerebral hypoperfusion (CCH) in a bilateral common carotid artery stenosis (BCAS) and hyperlipidemia mouse model of subcortical vascular dementia (SVaD).

Apolipoprotein E (ApoE)-deficient mice were subjected to either intermittent fasting in a form of time-restricted feeding for 6 hr per day or ad libitum feeding 2 months after BCAS surgery. Mice behavioral assessments (locomotion, spatial working memory, and recognition memory) were performed during the 1-month IF treatment period before the analyses of histopathological findings (astrogliosis, neuronal loss, white matter damage) and brain microcirculation (microvessel density and blood-brain barrier (BBB) integrity).

IF significantly ameliorated the decline in spatial working memory and recognition memory initially observed in SVaD mouse model. These enhancement in performances after IF intervention were paralleled by the preservation of hippocampal neuronal density in the ApoE-deficient BCAS mice, but further increase in astrogliosis was observed. The findings of cognitive improvements and neuroprotection in IF-treated mice suggest that fasting can be a potential nonpharmacological mean for the remediation of SVaD. This study may stimulate future investigations on the possible neuroprotective effects of fasting across many neurological diseases.