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Updated: May 1, 2026
A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
Published on: March 17, 2016
Recognition memory impairments after subcortical white matter stroke in mice
Francesco Blasi1, Ying Wei, Mustafa Balkaya
1From the Stroke and Neurovascular Research Laboratory, Department of Radiology (F.B., Y.W., M.B., C.A., M.A.M.), Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology (C.A.), Department of Cell Biology (S.T.), and Department of Radiology, Martinos Center for Biomedical Imaging (J.B.M.), Massachusetts General Hospital, Harvard Medical School, Boston; and Department of Pharmacology, School of Pharmacy, University College Cork, Cork, Ireland (C.W.).
A new mouse model using endothelin-1 effectively simulates white matter stroke and cognitive deficits. NOTCH3 gene deficiency worsened stroke severity and cognitive impairment in these models.
Area of Science:
- Neuroscience
- Stroke Research
- White Matter Pathology
Background:
- Small subcortical white matter infarcts are a frequent stroke type linked to cognitive decline.
- Limited models of white matter stroke hinder pathophysiology research.
Purpose of the Study:
- To investigate tissue and functional outcomes of ischemic lesions in the corpus callosum.
- To compare outcomes in wild-type (WT) mice and NOTCH3 knockout mice.
Main Methods:
- Stereotactic microinjections of endothelin-1 induced focal ischemic lesions in periventricular white matter.
- MRI confirmed infarct location; histology assessed lesion size.
- Behavioral deficits were evaluated in WT mice up to 1 month post-stroke.
Main Results:
- Ischemic damage included early blood flow deficits, blood-brain barrier opening, and white matter lesions.
- Later stages showed myelin/axonal degeneration and immune cell infiltration.
- NOTCH3 knockout mice exhibited larger infarcts and more severe cognitive deficits at 7 days.
Conclusions:
- Endothelin-1 microinjections provide a useful model for studying focal white matter infarcts and cognitive deficits.
- NOTCH3 deficiency exacerbates white matter stroke susceptibility and short-term outcomes.
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