Abstract WMP76: Long-Term Effects of Intracerebral Hemorrhage on Behavior and Inflammation

Abstract

Introduction: Intracerebral hemorrhage (ICH) survivors remain at high risk for progressive cognitive impairment and post-stroke depression. However, little is known about the contribution of chronic neuroinflammation and sex-specific differences to behavioral changes at late timepoints. Methods: ICH was induced in 3-month male and female C57BL/6J wild type mice by injecting 0.8μL of type VII collagenase into the right striatum. Mice were perfused on day 0 (naïve) and day 28 following ICH, and the perihematomal region harvested for microglia isolation on a FACSAria. Transcriptomics was analyzed using nCounter Digital Analyzer using a custom neuroinflammation panel. Social deficits and cognition were measured via the 3-chambered sociability test at 0, 28, and 60-days post-ICH. Results: GO Biological Processes revealed that type I interferon signaling genes comprised the top three upregulated gene sets (adjusted P value < 10 -5 ) when compared to naïve microglia, suggesting a continued inflammatory response 28 days following ICH. As expected, behavioral analysis showed no sociability differences between males (N=4) and females (N=3) at day 0 (p = 0.1313). Males did not show an overall decline in sociability at day 28 or day 60 when compared to day 0 (p > 0.05, N= 5, 4). However, females showed a progressive decrease in sociability that became significant at day 60 (p = 0.032, N= 3). Interestingly, females spent significantly less time with the novel mouse (p = 0.019) and more time in the nonsocial chambers when compared to males at day 60 (p = 0.030). Conclusions: Our findings suggest that there is a chronic inflammatory signature long after the initial cell response to ICH which may be promoting long-term behavioral deficits in a sex-specific manner. As type I interferons have been increasingly linked to mood disorders, understanding the relationship between chronic inflammation, mood, and sex-specific differences will be crucial.