Abstract WP144: Inflammation After Intracerebral Hemorrhage Is Locally Mediated

Abstract

Introduction: Secondary injury due to neuroinflammation poses a target in ICH research. We have demonstrated elevated serum IL-12 levels in rodents with cardiometabolic syndrome with hypertension compared with normotensive rodents. As hypertension is a risk factor in ICH, it is critical to understand whether there are also local cerebral changes in pro-inflammatory cytokines to explore targets for therapeutics. Methods: A pilot study of autologous-injection ICH was induced in (mREN2)27 (n=7) and control Hanover Sprague-Dawley (SD) (n=7) rats. Animals underwent tail-cuff blood pressure measurement, pre- and post-ICH neurobehavioral testing, and serum cytokine measurements. Sacrifice with brain harvest was performed at 24h and 7h post-ICH. Homogenization of the brain with quantitative measurement of hemoglobin and IL-12 concentrations was performed. Results: IL-12 peaked in the ipsilateral hemisphere in both SD and mREN rats at 24h post-ICH. There was a significant difference in local IL-12 levels between the ipsilateral and contralateral hemispheres at 72h, with minimal IL-12 elevation in the contralateral hemisphere (p=0.05) (Figure 1). Additionally, there was high correlation between hematoma size and IL-12 local expression. While there was no difference in cerebral IL-12 levels between strains, there was a significant elevation in baseline IL-12 serum levels in mREN compared to SD rats, and a trend towards serum elevation at 72h post-ICH. Conclusions: Cerebral IL-12 levels ipsilateral to ICH are significantly elevated compared to contralateral levels and peak 24h post-ICH. While serum IL-12 levels are elevated in rats with cardiometabolic syndrome, this is not seen in brain tissue following ICH. With the high correlation between hematoma size and IL-12 expression, these findings implicate macrophage recruitment from the hematoma as a driver of neuroinflammation and potential therapeutic target to augment surgical interventions for ICH.