Up to 30% of all strokes in humans occur as infarcts in the white matter. These produce specific stroke impairments, such as weakness on one side of the body. White matter strokes can also be initially clinically silent, but accumulate over time to produce dementia. There have been few studies of the molecular and cellular mechanisms of white matter stroke damage and repair. The basic research in this area has been limited because of the difficulty in establishing an animal model of subcortical white matter stroke in the rodent. We have recently developed a model of subcortical/white matter stroke in the mouse. This stroke produces damage below the forelimb motor cortex that is similar in location and size to many human white matter strokes.
This stroke produces a focus of cell death in white matter, and a response of reactive astrocytes and increased oligodendrocyte precursor cells (OPCs). When the stroke site is labeled for mouse immunglobulin, (green) the area of blood brain barrier breakdown can be seen in the background of neurofilament staining (red) (photo courtesy of Dr. Jason Hinman).
In the below figure the stroke is surrounded by reactive astrocytes (light blue) with a dense rim of NG2 positive (red) oligodendrocyte precursors (OPCs). OPCs are also labeled as green, in this specific transgenic reporter mouse line.
When this stroke is produced in a mouse line that is transgenic for cytosolic YFP expression in neurons (YFP H line), the trajectory and interruption of axons through the stroke site is apparent. This can be seen in the header photo for this page. Retraction bulbs are formed from axons that are transected by the stroke. In this figure the normal structure of axons in white matter is seen on the left panel. The site of the stroke, 7 days after the infarct, is seen in the right panel, and demarcated by an asterisk.
White matter stroke in the aged mouse produce lasting motor deficits (Rosenzweig and Carmichael, 2013).
Studies in this project in the Carmichael lab will determine the molecular systems that underlie OPC responses to stroke, the cellular processes that lead to possible re-myelination or axonal stabilization near areas of white matter damage, and how these processes affect motor recovery.