Pu Tinglin, Zou Wenyan, Feng Weixi, Zhang Yanli, Wang Linmei, Wang Hongxing, Xiao Ming
Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing 211166, China.
Deptment of Rehabilitation Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Exp Neurobiol. 2019 Feb;28(1):104-118. doi: 10.5607/en.2019.28.1.104. Epub 2019 Feb 28.
Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular event that often is followed by permanent brain impairments. It is necessary to explore the pathogenesis of secondary pathological damages in order to find effective interventions for improving the prognosis of SAH. Blockage of brain lymphatic drainage has been shown to worsen cerebral ischemia and edema after acute SAH. However, whether or not there is persistent dysfunction of cerebral lymphatic drainage following SAH remains unclear. In this study, autologous blood was injected into the cisterna magna of mice to establish SAH model. One week after surgery, SAH mice showed decreases in fluorescent tracer drainage to the deep cervical lymph nodes (dcLNs) and influx into the brain parenchyma after injection into the cisterna magna. Moreover, SAH impaired polarization of astrocyte aquaporin-4 (AQP4) that is a functional marker of glymphatic clearance and resulted in accumulations of Tau proteins as well as CD3, CD4, and CD8 cells in the brain. In addition, pathological changes, including microvascular spasm, activation of glial cells, neuroinflammation, and neuronal apoptosis were observed in the hippocampus of SAH mice. Present results demonstrate persistent malfunction of glymphatic and meningeal lymphatic drainage and related neuropathological damages after SAH. Targeting improvement of brain lymphatic clearance potentially serves as a new strategy for the treatment of SAH.
蛛网膜下腔出血（SAH）是一种毁灭性的脑血管事件，常伴有永久性脑损伤。有必要探索继发性病理损伤的发病机制，以寻找改善SAH预后的有效干预措施。急性SAH后，脑淋巴引流受阻会加重脑缺血和水肿。然而，SAH后是否存在持续性脑淋巴引流功能障碍仍不清楚。在本研究中，将自体血注入小鼠的小脑延髓池以建立SAH模型。术后一周，SAH小鼠在向小脑延髓池注射荧光示踪剂后，示踪剂向颈深淋巴结（dcLNs）的引流减少，进入脑实质的量也减少。此外，SAH损害了星形胶质细胞水通道蛋白4（AQP4）的极化，AQP4是类淋巴系统清除功能的功能性标志物，导致脑内Tau蛋白以及CD3、CD4和CD8细胞的积聚。此外，在SAH小鼠的海马体中观察到了包括微血管痉挛、胶质细胞活化、神经炎症和神经元凋亡在内的病理变化。目前的结果表明，SAH后类淋巴系统和脑膜淋巴引流持续功能障碍以及相关的神经病理损伤。靶向改善脑淋巴清除可能是治疗SAH的一种新策略。
