Abstract WP105: A Novel Mouse Model of Cerebellar Stroke With Hippocampal Deficits

Abstract

Objective: Each year in the U.S. there are an estimated 20,000 strokes resulting in cerebellar infarction. The neurological impairments observed in these patients include motor coordination and motor learning impairments. Surprisingly, cerebellar stroke patients also exhibit executive and emotional dysfunction. Establishing a model of cerebellar stroke that recapitulates aspects of human cerebellar infarction will allow for us to perform mechanistic studies of brain injury and identify therapeutic targets to improve recovery in stroke patients. The goal of this study was to develop and characterize a photo-thrombotic mouse model of focal cerebellar stroke. Methods: Adult male and female mice were head-fixed in a stereotaxic frame, were administered Rose Bengal (150 ug/g) and the superior cerebellar artery was illuminated for 15 minutes with a cold white LED light source. Behavioral testing of motor and memory function was performed in mice subjected to sham procedure or photo-thrombosis at 7 days following surgery. Stereological analysis of lesion volume was performed at 1 and 7 days after surgery. Extracellular field recordings were performed in the CA1 region of the hippocampus to assess long-term potentiation (LTP). Results: Cerebellar stroke volumes were larger at 1 day (2.4 mm 3 ) than 7 days (0.964 mm 3 ), likely due to edema at the earlier time point. Lesion volumes were similar between males and females at both time points. Cerebellar infarction resulted in gait abnormality, motor incoordination and ipsilateral limb impairments. Memory impairments were also observed at 7 days after cerebellar stroke. Memory deficits correlate with contralateral hippocampal long-term plasticity impairments at 7 days after stroke. Conclusions: We have developed a reproducible model of cerebellar stroke that results in cerebellar infarction and associated motor impairments. Importantly, we alsoobserve memory deficits and have identified a molecular mechanism that we can target to improve memory function after stroke. This novel model will be a valuable tool for understanding how alterations in the cerebellar network resulting from cerebellar infarction produce motor and non-motor deficits.