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小胶质细胞在蛛网膜下腔出血损伤及预后中的关键作用。

The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage.

作者信息

Ning Wenjing, Lv Shi, Wang Qian, Xu Yuzhen

机构信息

Department of Rehabilitation, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong Province, China.

Department of Central Laboratory, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong Province, China.

出版信息

Neural Regen Res. 2025 Jul 1;20(7):1829-1848. doi: 10.4103/NRR.NRR-D-24-00241. Epub 2024 Jul 10.

Abstract

Subarachnoid hemorrhage leads to a series of pathological changes, including vascular spasm, cellular apoptosis, blood-brain barrier damage, cerebral edema, and white matter injury. Microglia, which are the key immune cells in the central nervous system, maintain homeostasis in the neural environment, support neurons, mediate apoptosis, participate in immune regulation, and have neuroprotective effects. Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage. Moreover, microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage. Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury. This provides new targets and ideas for the treatment of subarachnoid hemorrhage. However, an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking. This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm, neuroinflammation, neuronal apoptosis, blood-brain barrier disruption, cerebral edema, and cerebral white matter lesions. It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage. Currently, microglia in subarachnoid hemorrhage are targeted with TLR inhibitors, nuclear factor-κB and STAT3 pathway inhibitors, glycine/tyrosine kinases, NLRP3 signaling pathway inhibitors, Gasdermin D inhibitors, vincristine receptor α receptor agonists, ferroptosis inhibitors, genetic modification techniques, stem cell therapies, and traditional Chinese medicine. However, most of these are still being evaluated at the laboratory stage. More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.

摘要

蛛网膜下腔出血会导致一系列病理变化,包括血管痉挛、细胞凋亡、血脑屏障损伤、脑水肿和白质损伤。小胶质细胞是中枢神经系统中的关键免疫细胞,维持神经环境的稳态,支持神经元,介导细胞凋亡,参与免疫调节,并具有神经保护作用。越来越多的证据表明,小胶质细胞在蛛网膜下腔出血的发病机制中起关键作用,并影响损伤过程和蛛网膜下腔出血的预后。此外,小胶质细胞在蛛网膜下腔出血的恢复阶段发挥一定的神经保护作用。几种旨在调节小胶质细胞功能的方法被认为可以减轻蛛网膜下腔出血损伤。这为蛛网膜下腔出血的治疗提供了新的靶点和思路。然而,目前仍缺乏对蛛网膜下腔出血后小胶质细胞作用的深入全面总结。本综述描述了蛛网膜下腔出血后小胶质细胞的激活及其在血管痉挛、神经炎症、神经元凋亡、血脑屏障破坏、脑水肿和脑白质病变等病理过程中的作用。还讨论了小胶质细胞在蛛网膜下腔出血恢复过程中的神经保护作用以及针对蛛网膜下腔出血后调节小胶质细胞功能的治疗进展。目前,针对蛛网膜下腔出血中的小胶质细胞,使用了Toll样受体(TLR)抑制剂、核因子-κB和信号转导和转录激活因子3(STAT3)通路抑制剂、甘氨酸/酪氨酸激酶、NLRP3信号通路抑制剂、Gasdermin D抑制剂、长春新碱受体α受体激动剂、铁死亡抑制剂、基因编辑技术、干细胞疗法和中药。然而,其中大多数仍处于实验室评估阶段。需要更多关于蛛网膜下腔出血的临床研究和数据来改善蛛网膜下腔出血的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deac/11691474/19d7cf0f9169/NRR-20-1829-g001.jpg

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