Abstract

Stroke remains the fifth leading cause of death in the U.S, highlighting a pressing need to improve the translatability of experimental stroke studies. To more reproducibly mimic clinical assessments in animal stroke models, we developed and tested a novel behavioral Neuroscore assessment designed to serve as an experimental analog to the National Institutes of Health Stroke Scale. Our Neuroscore measured discrepancies in visual, sensorimotor, and fatigue-related performances over five tasks while generating a numerical score ranging from zero to eleven (zero representing normal). Once administered, the resulting score was used as a predictor for determining the severity of stroke. The Neuroscore was designed and administered on C57Bl/6 mice. To mimic the NIH Stroke Scale, the Neuroscore used similar, but mouse-appropriate components over five-minute administrations: Level of Consciousness, Gaze and Visual Field, Sensory-Limb testing in response to stimuli, and a motor component assessed with Paralysis-Paw Hang tasks. Inter-rater reliability assessments were also performed. For this initial experiment, the MCAo model (tandem common carotid/middle cerebral artery occlusion model) was tested. Neuroscore effectively and significantly increased on post-stroke day (PSD) 1 after MCAo (N=36) compared to shams (N=25, p<0.001). Upon analyzing inter-rater reliability, a significant intraclass correlation coefficient of 0.707 was calculated (N=3, p<0.001). In conclusion, we developed a novel Neuroscore evaluation to mimic the NIH Stroke Scale for mice. The Neuroscore appropriately changed after experimental stroke, and significant reliability findings indicated similar scoring across experimenters. Future testing in other stroke models, as well as in rats is indicated to further evaluate this tool as a universal post-stroke translational assessment.

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