Publications (2)7.68 Total impact
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Article: Models that matter: white matter stroke models.
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ABSTRACT: Stroke is a devastating neurological disease with limited functional recovery. Stroke affects all cellular elements of the brain and impacts areas traditionally classified as both gray matter and white matter. In fact, stroke in subcortical white matter regions of the brain accounts for approximately 30% of all stroke subtypes, and white matter injury is a component of most classes of stroke damage. However, most basic scientific information in stroke cell death and neural repair relates principally to neuronal cell death and repair. Despite an emerging biological understanding of white matter development, adult function, and reorganization in inflammatory diseases, such as multiple sclerosis, little is known of the specific molecular and cellular events in white matter ischemia. This limitation stems in part from the difficulty in generating animal models of white matter stroke. This review will discuss recent progress in studies of animal models of white matter stroke, and the emerging principles of cell death and repair in oligodendrocytes, axons, and astrocytes in white matter ischemic injury.Journal of the American Society for Experimental NeuroTherapeutics 02/2012; 9(2):349-58. · 5.38 Impact Factor -
Article: A white matter stroke model in the mouse: axonal damage, progenitor responses and MRI correlates.
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ABSTRACT: Subcortical white matter stroke is a common stroke subtype but has had limited pre-clinical modeling. Recapitulating this disease process in mice has been impeded by the relative inaccessibility of the subcortical white matter arterial supply to induce white matter ischemia in isolation. In this report, we detail a subcortical white matter stroke model developed in the mouse and its characterization with a comprehensive set of MRI, immunohistochemical, neuronal tract tracing and electron microscopic studies. Focal injection of the vasoconstrictor endothelin-1 into the subcortical white matter produces an infarct core that develops a maximal MRI signal by day 2, which is comparable in relative size and location to human subcortical stroke. Immunohistochemical studies indicate that oligodendrocyte apoptosis is maximal at day 1 and apoptotic cells extend away from the stroke core into the peri-infarct white matter. The amount of myelin loss exceeds axonal fiber loss in this peri-infarct region. Activation of microglia/macrophages takes place at 1 day after injection near injured axons. Neuronal tract tracing demonstrates that subcortical white matter stroke disconnects a large region of bilateral sensorimotor cortex. There is a robust glial response after stroke by BrdU pulse-labeling, and oligodendrocyte precursor cells are initiated to proliferate and differentiate within the first week of injury. These results demonstrate the utility of the endothelin-1 mediated subcortical stroke in the mouse to study post-stroke repair mechanisms, as the infarct core extends through the partially damaged peri-infarct white matter and induces an early glial progenitor response.Journal of neuroscience methods 04/2009; 180(2):261-72. · 2.30 Impact Factor
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Institutions
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2009–2012
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University of California, Los Angeles
- Department of Neurology
Los Angeles, CA, USA
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