Abstract T P417: Remote Ischemic Post Conditioning (RIPostC) Is Effective In A Mouse Model Of Vascular Cognitive Impairment

Abstract

Background and Purpose: The mouse bilateral common carotid artery stenosis (BCAS) model is regarded as the best animal model for vascular cognitive impairment (VCI). RIPostC is a simple and safe therapy that others and we found protective in ischemic stroke. Other than risk factor control, there are no established treatments for VCI. However observational studies suggest exercise may be effective in patients with leukoaraiosis and cognitive impairment, the major form of VCI. Since RIPostC and exercise share some common mechanisms of action, we hypothesized that RIPostC would be effective in the mouse BCAS model and in VCI. Methods: Adult C57BL/6J male mice of (10-weeks) were subjected to either Sham for BCAS or BCAS surgery using micro coils twined around common carotid arteries. We randomized BCAS mice to daily RIPostC or sham procedure for RIPostC beginning 7 days post-BCAS for 2 weeks until day 21. Cerebral blood flow (CBF) was measured by laser speckle contrast imager. All mice underwent blinded testing for cognitive functions using novel object recognition (NOR). Histopathological examination and beta amyloid contents were investigated in the brain at day 30 post-BCAS. Statistical significance was determined at p <0.05. Results: At 1 hour, CBF was decreased significantly in all animals subjected to BCAS. RIPostC improved CBF in comparison to sham-operated group for RIPostC at day 14 and 28 post-VCI (p<0.05). BCAS impaired the discrimination index of mice in the NOR test but this was improved in the BCAS group treated with RIPostC (p<.05). Histopathological studies revealed that BCAS caused frequent vacuolization, cell death, microglial activation, loss in white matter (WM) and increased accumulation of beta amyloid. This was all attenuated significantly with RIPostC. Conclusions: RIPostC improves CBF, cognition and reduces cell death, WM damage and beta amyloid accumulation in the mouse BCAS model. Chronic RIPostC-therapy might be an effective treatment for VCI and in patients with leukoaraiosis and cognitive impairment Key words: RIPostC, VCI, white matter, beta-amyloid