Abstract WMP117: Effects Of Chronic Remote Ischemic Conditioning In A VCID Mouse Appears RBCNOS3 Dependent

Background and Purpose: Chronic remote ischemic conditioning (C-RIC) is effective at improving cerebral blood flow (CBF) inducing vascular remodeling, and improving cognition in a bilateral carotid artery stenosis (BCAS) mouse model, a model for Vascular Cognitive Impairment and Dementia (VCID). This augmentation is associated with increases of plasma nitrite. Our aim was to determine if the beneficial effect of C-RIC was red blood cell (NOS3) dependent. Methods: Microcoil (01.8 mm) induced BCAS model was used to induce chronic hypoperfusion. Aged RBCNOS3-KO and its control groups, NOS3flox-flox male mice (>12 months ) were randomly assigned to Sham RIC and RIC of both strains. RIC was started 7d post-surgery daily for 4 weeks. Behavioral test and CBF was performed before termination. Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire and beam walk test for motor/muscular impairment. Histopathological staining was also assessed of the brain tissues. Results: C-RIC-therapy for 4 weeks did not improve CBF in the RBCNOS3KO groups at 4 th weeks compared to ShamRIC groups. However, C-RIC therapy for 4 weeks significantly improved CBF in NOS3flox-flox groups compared to ShamRIC groups. Similarly, there was no significant change in the RBCNOS3 KO mice between the ShamRIC and RIC groups in the discrimination index/exploration time as determined by the NOR test or poor motor function as determined by hanging wire and beam walk test whereas the NOS3flox-flox mice did show improved cognition with RIC. Conclusions: The beneficial effect of C-RIC in the BCAS model is abrogated in RBCNOS3 KO mice indicating that the effect of C-RIC is NOS3 dependent.