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Neuroprotection by Mesenchymal Stem Cell (MSC) Administration is Enhanced by Local Cooling Infusion (LCI) in Ischemia.

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机构： [a]China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing 100053, China [b]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China [c]Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA [d]Department of Research & Development Center, John D. Dingell VA Medical Center, Detroit, MI, USA

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The present study aimed to determine if hypothermia augments the neuroprotection conferred by MSC administration by providing a conducive micro-environment. Sprague-Dawley rats were subjected to 1.5 h middle cerebral artery occlusion (MCAO) followed by 6 or 24 h of reperfusion for molecular analyses, as well as 1, 14 and 28 days for brain infarction or functional outcomes. Rats were treated with either MSC (1×105), LCI (cold saline, 0.6 ml/min, 5min) or both. Brain damage was determined by Infarct volume and neurological deficits. Long-term functional outcomes were evaluated using foot-fault and Rota-rod testing. Human neural SHSY5Y cells were investigated in vitro using 2 h oxygen-glucose deprivation (OGD) followed by MSC with or without hypothermia (HT) (34°C, 4 h). Mitochondrial transfer was assessed by confocal microscope, and cell damage was determined by cell viability, ATP, and ROS level. Protein levels of IL-1β, BAX, Bcl-2, VEGF and Miro1 were measured by Western blot following 6 h and 24 h of reperfusion and reoxygenation. MSC, LCI, and LCI+MSC significantly reduced infarct volume and deficit scores. Combination therapy of LCI+MSC precipitated better long-term functional outcomes than monotherapy. Upregulation of Miro1 in the combination group increased mitochondrial transfer and lead to a greater increase in neuronal cell viability and ATP, as well as a decrease in ROS. Further, combination therapy significantly decreased expression of IL-1β and BAX while increasing Bcl-2 and VEGF expression. Therapeutic hypothermia upregulated Miro1 and enhanced MSC mitochondrial transfer-mediated neuroprotection in ischemic stroke. Combination of LCI with MSC therapy may facilitate clinical translation of this approach. Copyright © 2019. Published by Elsevier B.V.

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出版当年[2018]版：

大类 | 3 区医学

小类 | 3 区神经科学

最新[2023]版：

大类 | 4 区医学

小类 | 4 区神经科学

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出版当年[2017]版：

Q2 NEUROSCIENCES

最新[2023]版：

Q3 NEUROSCIENCES

影响因子： 2.7 最新[2023版] 2.9 最新五年平均 3.125 出版当年[2017版] 2.929 出版当年五年平均 2.746 出版前一年[2016版] 2.929 出版后一年[2018版]

第一作者：

第一作者机构： [a]China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing 100053, China [b]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China [c]Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA [d]Department of Research & Development Center, John D. Dingell VA Medical Center, Detroit, MI, USA

通讯作者：

通讯机构： [a]China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing 100053, China [b]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China [*1]China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

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