Autologous bone marrow mononuclear cells enhance recovery after acute ischemic stroke in young and middle-aged rats.

Autologous bone marrow mononuclear cells enhance recovery after acute ischemic stroke in young and middle-aged rats.
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DOI:
10.1038/jcbfm.2009.198
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发表时间:
2010-01
期刊:
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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我们研究了动脉内注射自体骨髓单个核细胞(MNCs)治疗急性缺血性卒中大鼠。Long Evans大鼠(2 - 3月龄或12月龄)进行串联可逆性颈总动脉(CCA)/大脑中动脉(MCA)闭塞(CCAo/MCAo)3 h,然后24 h后进行胫骨骨髓收获。通过颈动脉内输注再注射一千万或四百万个细胞。对照组动物接受骨髓针插入,然后向颈动脉注射生理盐水。对动物进行一系列神经系统测试。使用Q-dot荧光标记追踪缺血脑中的MNCs。分析了受缺血影响的大脑中的梗死体积和细胞因子。与溶剂治疗的动物相比,年轻组和老年组的细胞治疗动物在中风后7 - 30天表现出改善。与生理盐水相比,MNCs显著减少梗死体积。与生理盐水对照组相比,从细胞处理组收集的损伤脑中肿瘤坏死因子-α、白细胞介素-1 α(IL-1α)、IL-β、IL-6显著降低,而IL-10显著升高。标记的MNCs被发现在梗死周围区域在1小时,并在随后的一周注射后呈指数下降。自体骨髓MNC可以安全地从中风后的啮齿动物中获得,迁移到梗死周围区域,促进恢复,并调节缺血后炎症反应。
We investigated intra-arterially administered autologous bone marrow mononuclear cells (MNCs) in rats with acute ischemic stroke. Long Evans rats (2 to 3 months or 12 months old) underwent tandem reversible common carotid artery (CCA)/middle cerebral artery (MCA) occlusion (CCAo/MCAo) for 3 h and then 24 h later underwent tibial bone marrow harvest. Ten million or 4 million cells were re-injected by an intra-carotid infusion. Control animals underwent marrow needle insertion and then saline injection into the carotid artery. Animals were assessed on a battery of neurological tests. MNCs in the ischemic brain were tracked using Q-dot nanocrystal labeling. Infarct volume and cytokines in the ischemia-affected brain were analyzed. Cell-treated animals in the younger and older groups showed improvement from 7 to 30 days after stroke compared with vehicle-treated animals. MNCs significantly reduced infarct volume compared with saline. There was a significant reduction in tumor necrosis factor-α, interleukin-1α (IL-1α), IL-β, IL-6, and a significant increase in IL-10 in injured brains harvested from the cell-treated groups compared with saline controls. Labeled MNCs were found in the peri-infarcted area at 1 h and exponentially decreased over the ensuing week after injection. Autologous bone marrow MNCs can be safely harvested from rodents after stroke, migrate to the peri-infarct area, enhance recovery, and modulate the post-ischemic inflammatory response.
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