Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
Sichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
Oxid Med Cell Longev. 2022 Aug 17;2022:6422202. doi: 10.1155/2022/6422202. eCollection 2022.
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.
最近的脑血管再通治疗临床试验已经验证了在传统时间窗之外的患者中的延迟再通。然而，关于延迟再通的病理生理学和良好结果的信息仍然很少。由于巨噬细胞在组织修复中得到了广泛的研究，我们预计它们可能在缺血性卒中后的延迟再通中发挥关键作用。
在成年雄性 Sprague-Dawley 大鼠中，使用了两种缺血性卒中组：永久性大脑中动脉闭塞（pMCAO）和大脑中动脉闭塞后 3 天的延迟再通（rMCAO）。为了评估结果，报告了脑形态、神经功能、巨噬细胞浸润、血管生成和神经退行性变。为了证实巨噬细胞的作用，在耗尽它们之后，我们评估了延迟再通后的血管生成和神经退行性变。
pMCAO 和 rMCAO 组之间的出血率或动物死亡率没有显著差异。与未再通组相比，延迟再通增加了血管生成，减少了梗死体积和神经退行性变，并改善了神经功能结果。在 rMCAO 组中，巨噬细胞浸润促进了血管生成，其特征是血管内皮生长因子 A 和血小板衍生生长因子 B 的增加。证实了这些联系，巨噬细胞耗竭减少了血管生成、炎症、梗死周围区域的神经元存活以及延迟再通后的良好结果。
如果选择得当，梗死后第 3 天的延迟再通可以显著改善缺血性卒中后的神经功能结果。梗死/梗死周围区域的巨噬细胞暴露于血液中对于缺血性卒中后 3 天的延迟再通后的良好结果是必要的。
