418 CXCL-10 Influences Local Regulation of Neuroinflammation After Intracranial Hemorrhage

Abstract

INTRODUCTION: Mitigating secondary injury from neuroinflammation is a critical investigation to identify therapeutic targets and improve ICH outcomes. Plasma CXCL10, a chemokine of chemo-attraction for monocytes/macrophages, T cells, and NK cells, is significantly elevated in hypertensive patients; therefore, we investigated the role of CXCL10 in local neuro-inflammation after hypertensive ICH. Furthermore, it is also vital to understand the local effects of common risk factors of ICH such as hypertension and cardiometabolic disease on pro-inflammatory chemokines. METHODS: A pilot study of autologous-injection ICH was induced in hypertensive (mREN2)7 (n = 5) and normotensive Hanover Sprague-Dawley male rats (n = 5). Tail-cuff blood pressure measurements and pre- and post-ICH neurobehavioral testing was performed. Rat sacrifice was performed at 5 days post-ICH with subsequent homogenization of hematoma area and contralateral area (2 mm brain slice around injection site). Hemoglobin was measured using whole hemispheres, but small slices were used for assessing immune inflammation. Lastly, qPCR testing was performed to determine CXCL-10 level of expression. RESULTS: CXCL-10 was significantly different in the local ipsilateral hemisphere of both the cardiometabolic mREN model (P = 0.012) and control SD (P = 0.025) rats compared to the contralateral hemisphere at 5 days post-ICH. There was no significant difference in CXCL-10 expression between SD and mREN rat models in contralateral or ipsilateral hemispheres. CONCLUSIONS: Cerebral CXCL-10 levels ipsilateral to ICH are significantly elevated compared to the contralateral hemisphere indicating the locally injured brain tissue expressed CXCL-10 to recruit immunocyte infiltration. CXCL-10 elevation does not appear to be influenced by comorbidities of cardiometabolic disease or hypertension. These results implicate CXCL-10 mediated processes such as activation and recruitment of leukocytes in post-ICH secondary injury, which may prove to be an important therapeutic target.