Human neural stem cells improve early stage stroke outcome in delayed tissue plasminogen activator-treated aged stroke brains

Experimental Neurology
Austin C BoeseJean-Pyo Lee

Abstract

Clinically, significant stroke injury results from ischemia-reperfusion (IR), which induces a deleterious biphasic opening of the blood-brain barrier (BBB). Tissue plasminogen activator (tPA) remains the sole pharmacological agent to treat ischemic stroke. However, major limitations of tPA treatment include a narrow effective therapeutic window of 4.5 h in most patients after initial stroke onset and off-target non-thrombolytic effects (e.g., the risk of increased IR injury). We hypothesized that ameliorating BBB damage with exogenous human neural stem cells (hNSCs) would improve stroke outcome to a greater extent than treatment with delayed tPA alone in aged stroke mice. We employed middle cerebral artery occlusion to produce focal ischemia with subsequent reperfusion (MCAO/R) in aged mice and administered tPA at a delayed time point (6 h post-stroke) via tail vein. We transplanted hNSCs intracranially in the subacute phase of stroke (24 h post-stroke). We assessed the outcomes of hNSC transplantation on pathophysiological markers of stroke 48 h post-stroke (24 h post-transplant). Delayed tPA treatment resulted in more extensive BBB damage and inflammation relative to MCAO controls. Notably, transplantation of hNSCs ameliorate...Continue Reading

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Citations

Aug 31, 2020·Translational Stroke Research·Abir A RahmanGregory J Bix
Nov 4, 2020·Translational Stroke Research·Yinghua JiangXiaoying Wang
Jul 25, 2021·International Journal of Molecular Sciences·Milton H Hamblin, Jean-Pyo Lee
Oct 19, 2021·Frontiers in Pharmacology·Lijun YangQinjie Weng

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