Macrophage Infiltration Reduces Neurodegeneration and Improves Stroke Recovery after Delayed Recanalization in Rats.

Macrophage Infiltration Reduces Neurodegeneration and Improves Stroke Recovery after Delayed Recanalization in Rats.
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DOI:
10.1155/2022/6422202
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发表时间:
2022
影响因子:
--
通讯作者:
Jiang, Yong
Jiang, Yong
中科院分区:
生物学2区
文献类型:
--
作者:
Pang, Jinwei;Matei, Nathanael;Peng, Jianhua;Zheng, Wen;Yu, Jing;Luo, Xu;Camara, Richard;Chen, Ligang;Tang, Jiping;Zhang, John H.;Jiang, Yong

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Recent cerebrovascular recanalization therapy clinical trials have validated delayed recanalization in patients outside of the conventional window. However, a paucity of information on the pathophysiology of delayed recanalization and favorable outcomes remains. Since macrophages are extensively studied in tissue repair, we anticipate that they may play a critical role in delayed recanalization after ischemic stroke. In adult male Sprague-Dawley rats, two ischemic stroke groups were used: permanent middle cerebral artery occlusion (pMCAO) and delayed recanalization at 3 days following middle cerebral artery occlusion (rMCAO). To evaluate outcome, brain morphology, neurological function, macrophage infiltration, angiogenesis, and neurodegeneration were reported. Confirming the role of macrophages, after their depletion, we assessed angiogenesis and neurodegeneration after delayed recanalization. No significant difference was observed in the rate of hemorrhage or animal mortality among pMCAO and rMCAO groups. Delayed recanalization increased angiogenesis, reduced infarct volumes and neurodegeneration, and improved neurological outcomes compared to nonrecanalized groups. In rMCAO groups, macrophage infiltration contributed to increased angiogenesis, which was characterized by increased vascular endothelial growth factor A and platelet-derived growth factor B. Confirming these links, macrophage depletion reduced angiogenesis, inflammation, neuronal survival in the peri-infarct region, and favorable outcome following delayed recanalization. If properly selected, delayed recanalization at day 3 postinfarct can significantly improve the neurological outcome after ischemic stroke. The sanguineous exposure of the infarct/peri-infarct to macrophages was essential for favorable outcomes after delayed recanalization at 3 days following ischemic stroke.
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