Abstract TP285: Chronic Remote Ischemic Conditioning (C-RIC) and Physical Exercise Attenuate NLRP3 Inflammasome Activation Induced by Chronic Cerebral Hypoperfusion in the BCAS Mouse Model of VCID

Background and Purpose: Inflammation plays a significant role in acute and chronic cerebral ischemia. The bilateral carotid artery stenosis (BCAS)-induced chronic cerebral hypoperfusion activates the NLRP inflammasome in brain tissue. We aimed to determine if C-RIC and physical exercise (EXR) attenuated the increase in the NLRP3 inflammasome and related cytokines in the BCAS model. Methods: Microcoil-induced BCAS was used for chronic hypoperfusion, a model for VCID. Middle-young (5 months old) and old-aged (14 months old) C57Bl/6 mice were randomly assigned to Sham, BCAS, and BCAS+EXR (four weeks treadmill exercise) for middle-young mice and to Sham, BCAS, and BCAS+RIC (four months C-RIC treatment) for old-aged mice of both sexes. qPCR was run for NLRP3, TNFa, IL-1B, IL-6, IL-10, ICAM1, VCAM1 in brain tissue.Biochemical assays and histopathological staining of NLRP3 were also assessed on the brain tissues. Results: Four weeks of exercise in middle-aged mice and 4 months of C-RIC in aged RIC groups attenuated the increased NLRP3, cytokines (IL-1B, IL-6, IL-10, TNFα), and inflammatory markers (ICAM-1 & VCAM-1) induced by BCAS in middle-aged (exercise) and aged mice (CRIC). Western blot and immunohistopathological studies also attenuated the increased NLRP3 expression after physical exercise and C-RIC treatment. Conclusions: C-RIC and Physical exercise attenuated the increase of NLRP3 inflammasome and cytokines (IL-1B, IL-6, IL-10, TNFα) induced by chronic cerebral hypoperfusion in the BCAS mouse model of VCID. This may be an important mechanism of action of physical exercise and C-RIC in VCID.