Long-Term Motor Deficit and Diffuse Cortical Atrophy Following Focal Cortical Ischemia in Athymic Rats

Autor: Charlotte M. Ermine, Fahad Somaa, Ting-Yi Wang, Brett J. Kagan, Clare L. Parish, Lachlan H. Thompson
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Frontiers in Cellular Neuroscience, Vol 13 (2019)
Druh dokumentu: article
ISSN: 1662-5102
DOI: 10.3389/fncel.2019.00552
Popis: Development of new stroke therapies requires animal models that recapitulate the pathophysiological and functional consequences of ischemic brain damage over time-frames relevant to the therapeutic intervention. This is particularly relevant for the rapidly developing area of stem cell therapies, where functional replacement of circuitry will require maturation of transplanted human cells over months. An additional challenge is the establishment of models of ischemia with stable behavioral phenotypes in chronically immune-suppressed animals to allow for long-term survival of human cell grafts. Here we report that microinjection of endothelin-1 into the sensorimotor cortex of athymic rats results in ischemic damage with a sustained deficit in function of the contralateral forepaw that persists for up to 9 months. The histological post-mortem analysis revealed chronic and diffuse atrophy of the ischemic cortical hemisphere that continued to progress over 9 months. Secondary atrophy remote to the primary site of injury and its relationship with long-term cognitive and functional decline is now recognized in human populations. Thus, focal cortical infarction in athymic rats mirrors important pathophysiological and functional features relevant to human stroke, and will be valuable for assessing efficacy of stem cell based therapies.
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