Abstract WP417: Novel Animal Model for Cerebral Small Vessel Disease

Abstract

Introduction: Cerebral small vessel disease (SVD) is a common finding in patients with stroke. It can manifest as white matter hyperintensities (WMH), microbleeds or lacunar strokes. Presence of SVD is an independent risk factor for stroke and is considered a poor prognostic factor in stroke recovery. In addition, SVD has been associated with vascular dementia, depression and gait disorder. There are no good animal models to study SVD. Hypothesis: The precise mechanism behind development of SVD is not clearly understood. It’s likely a result of multiple different processes including decreased blood flow, inflammation with blood brain barrier disruption, degeneration and myelin breakdown. We try to study the role of reduced blood flow and inflammation in the development of SVD with the eventual goal of developing an agent that may prevent the development or progression of SVD. Methods: We remodeled a novel murine SVD model - asymmetric common carotid artery surgery (ACAS), published recently. We placed an ameroid constrictor around the right common carotid artery (CCA) which gradually narrows and eventually occludes vessels by releasing hygroscopic casein material, and a microcoil around the left CCA in mice. This model causes gradual narrowing of the vessels and a significant reduction of cerebral blood flow as detected by Laser Speckle Imager. These mice were compared to sham control which underwent a sham surgery without any vessel occlusion (n=7 per group). Animals were monitored for 30 days. Results: In the ACAS group, the model caused morbidity in all mice and death in 2 of 7 mice. Histologically, we observed marked vacuoles in white matter evaluated by H&E staining. We devised a severity score based on the extent of white matter damage and presence of infarcts under microscope. Based on this score, the damage was significantly worse in the ACAS group as compared with sham controls. Conclusions: These findings demonstrate the role of gradual blood flow reduction in development of SVD. We plan to further study the mechanisms behind SVD and develop novel treatments with the goal of preventing SVD.