Abstract WMP111: Microvascular Occlusion Precedes Delayed Deficits In Mice With Subarachnoid Hemorrhage

Abstract

Subarachnoid hemorrhage (SAH) induces delayed cerebral ischemia (DCI) in about 30% of patients which is characterized by functional decline. Microvascular occlusion, via microvessel constriction or microthrombi, may be a cause of DCI. Our hypothesis is that microvascular occlusion and reduced cerebral blood flow (CBF) precede the onset of delayed deficits in mice with SAH. Mice were randomly assigned into sham, SAH+saline, and SAH+A3P5P+Clopidogrel (platelet antagonists). Laser speckle imaging (to assess large and microvessel perfusion) and behavior were assessed daily. All outcomes were performed and data was analyzed by a blinded investigator. Both large artery and microvessel/tissue perfusion recover to baseline in SAH mice which do not get delayed deficits. However, in SAH mice which develop delayed deficits, microvessel/tissue perfusion has a prolonged reduction (Figure 1A). Interestingly, large artery perfusion recovers in these mice. Antiplatelets prevent microthrombi, attenuating microvessel occlusion, and reduce delayed deficits (Figure 2B-C). Our findings suggest that 1) microvessel occlusion and prolonged tissue perfusion are causative factors for DCI and 2) preventing platelet activation may be a therapeutic target to reduce the incidence of DCI. Our data also suggests a sex difference in the response to platelet antagonists (data not shown).