Stroke is the leading cause of adult disability due to the brain's limited functional recovery after injury. Stroke affects regions of the brain that contain neuronal cell bodies (gray matter) and those that contain their connections (white matter). To date, gray matter neuronal stroke has been well characterized. However, there are no animal models of subcortical white matter stroke.
Purpose The aims of the fellowship are to (1) develop a model for subcortical white matter stroke in the mouse, (2) determine the type of cell death after white matter stroke and compare it with gray matter stroke, and (3) characterize neuronal stem cell migration surrounding the infarct.
Methods Strokes were produced in the mouse white matter underlying the forelimb motor cortex using endothelin-1, a vasoconstrictor. After 5 days post-stroke, the brains were fixed, frozen-sectioned, and processed for markers of white matter and neuronal structure and injury: myelin basic protein (MBP), Ng2, glial fibrillary acid protein (GFAP), amyloid precursor protein (APP), microtubule associated protein 2 (MAP2), neurofilaments (NF200), doublecortin, and fractin (a marker of apoptosis) using immunohistochemical staining.
Results Based on different cohorts of animals, the methodology for this stroke model was systematically changed to optimize a small subcortical stroke. The concentration of endothelin-1 solution was adjusted from 0.4 μg/μL to 0.25 μg/μL. The stereotaxic dorsal/ventral and medial/lateral coordinates were altered to target the white matter without excessive bleeding and cortical damage. Additionally, the injection micropipette was left in place for 10 minutes after injection to prevent reflux.
Conclusions The model demonstrates (1) a reliable method for targeting white matter using microinjection of a vasoconstrictor, (2) increased oligodendrocyte precursor cells and increased axonal injury in the infarcted white matter, and (3) initially increased migrating neuroblasts in the area of white matter damage.
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