Abstract 46: The Influence of Age and Stroke on Gut Inflammation and Microbiota

Abstract

Introduction: Earlier work by our laboratory and other groups has identified that aging leads to changes in both the immune system and the microbiome. The elderly have high mortality and more disability after a stroke, a finding that is recapitulated in murine model. Recently, pro-inflammatory γδ T cells have received increasing attention as a major contributor to gut immune responses. These cells may be a link in the bidirectional communication between the microbiome and the central nervous system. We hypothesize that fecal transplant of aged biome into young animals will enhance inflammation, γδ T cell numbers, and worsen functional recovery after stroke in young mice. Methods: Young C57BL/6 male mice, were randomized and subjected to sham surgery/right middle cerebral artery occlusion (MCAO-60min) followed by reperfusion. All mice received streptomycin treatment at 24h and 48h after MCAO. Subsequently, mice were gavaged with biome from either young or aged animals at 72 and 96 h post-stroke. Behavioral and functional outcomes were evaluated. Animals were sacrificed 15 days after stroke. Brain atrophy was quantified, and Flow Cytometry (FACS) and immunohistochemistry was performed on gut tissue and spleen to determine if stroke or the aged biome influence γδ T cells. Results: Young mice transplanted with aged biome take a longer time to regain their pre-stroke body weight. These mice have higher post-stroke hyperactivity compared with mice treated with young biome, as measured by average velocity (p<.006) and total distance traveled (p<.006) in the Open Field. Young mice given aged biome had poorer grip strength, as well as a depressive phenotype, when compared with mice transplanted with young biome. FACS analysis shows higher levels of γδ T cell in the gut with stroke and with fecal transplant of aged biome (sham vs. stroke p=0.0443; young vs. aged biome p=0.0199). Conclusion: Collectively our findings suggests that the gut microbiome plays an important role in post-stroke recovery. Understanding the underlying mechanisms may identify novel therapeutic targets for the treatment of stroke patients.