1139 Role of Platelets in the Development of Neurological Deficits Resulting From Subarachnoid Hemorrhage in Mice

INTRODUCTION: Microthrombosis (platelet aggregation) has been suggested as a major factor contributing to delayed neurological deterioration in patients after subarachnoid hemorrhage (SAH). However, experimental studies on the role of microthrombi in delayed deficits after SAH have not been investigated in depth. Similarly, the only clinically existing antiplatelet therapy is nimodipine, with other therapies being invasive. METHODS: SAH was induced in adult male and female C57BL/6 mice via endovascular perforation. Mice were randomly assigned into sham (n=6/sex) or SAH groups (n=22-24/sex). A neurobehavior exam was performed on days 1-3, 5, and 7 post-SAH using a composite neuroscore. Animals were sacrificed on the day of delayed deficits or 7 days post-SAH. Microthrombi count and vessel diameters (for vasospasm) were measured using H&E stained brain slices. All outcomes were performed and all data were analyzed by a blinded investigator. RESULTS: Seventeen percent (4/24) of male mice and thirty-six percent (8/22) of female mice developed delayed deficits on days 3-5 post-SAH. Those mice which developed delayed deficits had significantly more microthrombi in their brains than mice which did not develop delayed deficits; vasospasm did not correlate with delayed deficits. Additionally, female SAH mice develop delayed deficits at a higher frequency than males. CONCLUSIONS: This work found that microthrombi correlated with delayed deficits. The data within this study suggests that preventing platelets and microthrombi may improve functional recovery and reduce the risk of delayed neurological deficits. Future directions include testing therapeutics such as tirofiban and other platelet antagonists.