Neuroprotection by mesenchymal stem cell (MSC) administration is enhanced by local cooling infusion (LCI) in ischemia
Neuroprotection by mesenchymal stem cell (MSC) administration is enhanced by local cooling infusion (LCI) in ischemia
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缺血时局部冷却输注（LCI）可增强间充质干细胞（MSC）给药的神经保护作用
DOI：
10.1016/j.brainres.2019.146406
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发表时间：
2019-12
期刊：
影响因子：
2.9
通讯作者：
Yuchuan Ding
中科院分区：
文献类型：
--
作者：
Wenjing Wei;Di Wu;Yunxia Duan;Kenneth B. Elkin;Ankush Ch;ra;Longfei Guan;Changya Peng;Xiaoduo He;Chuanjie Wu;Xunming Ji;Yuchuan Ding
本研究的目的是确定是否低温增强MSC管理所赋予的神经保护，通过提供一个有益的microenvironment.MethodsSprague-Dawley大鼠进行1.5小时大脑中动脉闭塞（MCAO），然后6或24小时的再灌注分子分析，以及1，14和28天的脑梗死或功能的结果。用MSC（1 × 105）、LCI（冷盐水，0.6ml/min，5 min）或两者处理大鼠。通过脑CT容积和神经功能缺损来确定脑损伤。使用足部故障和旋转棒测试评价长期功能结局。体外培养人神经SHSY 5 Y细胞，采用2 h氧-糖剥夺（OGD），然后用MSC伴或不伴低温（HT）（34 °C，4 h）。通过共聚焦显微镜评估线粒体转移，并通过细胞活力、ATP和ROS水平确定细胞损伤。结果MSC、LCI、LCI + MSC组再灌注6 h和24 h后，脑梗死体积和脑梗死体积分数均显著降低，脑梗死灶体积和脑梗死灶体积分数均显著降低，脑梗死灶体积和脑梗死灶体积分数均显著降低。LCI + MSC的联合治疗比单药治疗的长期功能结局更好。联合组中Miro 1的上调增加了线粒体转移，并导致神经元细胞活力和ATP的更大增加，以及ROS的减少。结论低温治疗可上调Miro 1的表达，增强MSC线粒体转移介导的缺血性脑卒中神经保护作用。LCI与MSC治疗的组合可以促进这种方法的临床转化。
ObjectiveThe present study aimed to determine if hypothermia augments the neuroprotection conferred by MSC administration by providing a conducive micro-environment.MethodsSprague-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, 5 min) 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 investigatedin vitrousing 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.ResultsMSC, 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.ConclusionTherapeutic 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.
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影响因子：
3.3
作者：
Chopp M;Steinberg GK;Kondziolka D;Lu M;Bliss TM;Li Y;Hess DC;Borlongan CV
通讯作者：
Borlongan CV
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DOI：
10.1177/0271678x18808174
发表时间：
2018-10
期刊：
J Cereb Blood Flow Metab
影响因子：
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作者：
Zhao J;Mu H;Liu L
通讯作者：
Liu L
DOI：
--
发表时间：
2015
期刊：
--
影响因子：
--
作者：
Theo Diamandis;C. Borlongan
通讯作者：
Theo Diamandis;C. Borlongan
DOI：
10.1083/jcb.201511036
发表时间：
2016-02-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mishra P;Chan DC
通讯作者：
Chan DC
热休克蛋白 27 的内皮靶向过度表达可改善缺血性脑损伤后血脑屏障的破坏
DOI：
10.1073/pnas.1621174114
发表时间：
2017-02-14
影响因子：
11.1
作者：
Shi, Yejie;Jiang, Xiaoyan;Chen, Jun
通讯作者：
Chen, Jun