Subcortical White Matter Stroke in the Mouse: Inducing Injury and Tracking Cellular Proliferation

Marin, Miguel A.; Gleichman, Amy J.; Brumm, Andrew J; Carmichael, S. Thomas

doi:10.1007/978-1-0716-2926-0_2

Cited by 1 publication

(2 citation statements)

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“…WMS was produced as previously described ( Hinman et al, 2015 ; Rosenzweig and Carmichael, 2015 ; Marin et al, 2023 ). The vasoconstrictor N5-(1-iminoethyl)-L-ornithine (27 mg/ml in 0.9% saline; EMD Millipore) was injected via micropipette through the cortex and into the white matter ventral to the motor cortex at an angle of 45 degrees (posterior to anterior).…”

Section: Methodsmentioning

confidence: 99%

“…An alternative approach was taken to colocalize EdU with HCR probes. EdU was administered as previously described ( Marin et al, 2023 ) Mice were administered EdU (Calbiochem) in their drinking water (200 µg/ml) and given ad libitum access through the duration of the experiment. Tissue was then processed for HCR labeling as previously described with an added EdU labeling and imaging step.…”

Section: Methodsmentioning

confidence: 99%

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Motor Activity-Induced White Matter Repair in White Matter Stroke

Marin,

Gleichman,

Wei

et al. 2023

J. Neurosci.

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Subcortical white matter stroke (WMS) is a progressive disorder which is demarcated by the formation of small ischemic lesions along white matter tracts in the central nervous system. As lesions accumulate, patients begin to experience severe motor and cognitive decline. Despite its high rate of incidence in the human population, our understanding of the cause and outcome of WMS is extremely limited. As such, viable therapies for WMS remain to be seen. This study characterizes myelin recovery following stroke and motor learning-based rehabilitation in a mouse model of subcortical WMS. Following WMS, a transient increase in differentiating oligodendrocytes occurs within the periinfarct in young male adult mice, which is completely abolished in male aged mice. Compound action potential recording demonstrates a decrease in conduction velocity of myelinated axons at the periinfarct. Animals were then tested on one of three distinct motor learning-based rehabilitation strategies (skilled reach, restricted access to a complex running wheel, and unrestricted access to a complex running wheel) for their capacity to induce repair. These studies determined that unrestricted access to a complex running wheel alone increases the density of differentiating oligodendrocytes in infarcted white matter in young adult male mice, which is abolished in aged male mice. Unrestricted access to a complex running wheel was also able to enhance conduction velocity of myelinated axons at the periinfarct to a speed comparable to naive controls suggesting functional recovery. However, there was no evidence of motor rehabilitation-induced remyelination or myelin protection.Significance StatementWhite matter stroke is a common disease with no medical therapy. A form of motor rehabilitation improves some aspects of white matter repair and recovery.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%