The Translational Research Institute for Neurological Disorders of Wannan Medical College, Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), No. 2 West Zheshan Road, Wuhu, 241001, Anhui, China; The Institutes of Brain Science, Wannan Medical College, No. 22 Wenchang West Road, Higher Education Park, Wuhu, 241002, Anhui, China.
The Translational Research Institute for Neurological Disorders of Wannan Medical College, Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), No. 2 West Zheshan Road, Wuhu, 241001, Anhui, China.
Neuropharmacology. 2024 Jun 15;251:109896. doi: 10.1016/j.neuropharm.2024.109896. Epub 2024 Mar 13.
Secondary brain injury after intracerebral hemorrhage (ICH) is the main cause of poor prognosis in ICH patients, but the underlying mechanisms remain less known. The involvement of Piezo1 in brain injury after ICH was studied in a mouse model of ICH. ICH was established by injecting autologous arterial blood into the basal ganglia in mice. After vehicle, Piezo1 blocker, GsMTx4, Piezo1 activator, Yoda-1, or together with mannitol (tail vein injection) was injected into the left lateral ventricle of mouse brain, Piezo1 level and the roles of Piezo1 in neuronal injury, brain edema, and neurological dysfunctions after ICH were determined by the various indicated methods. Piezo1 protein level in neurons was significantly upregulated 24 h after ICH in vivo (human and mice). Piezo1 protein level was also dramatically upregulated in HT22 cells (a murine neuron cell line) cultured in vitro 24 h after hemin treatment as an in vitro ICH model. GsMTx4 treatment or together with mannitol significantly downregulated Piezo1 and AQP4 levels, markedly increased Bcl2 level, maintained more neurons alive, considerably restored brain blood flow, remarkably relieved brain edema, substantially decreased serum IL-6 level, and almost fully reversed the neurological dysfunctions at ICH 24 h group mice. In contrast, Yoda-1 treatment achieved the opposite effects. In conclusion, Piezo1 plays a crucial role in the pathogenesis of brain injury after ICH and may be a target for clinical treatment of ICH.
脑出血（ICH）后的继发性脑损伤是导致 ICH 患者预后不良的主要原因，但发病机制尚不清楚。本研究旨在探讨 Piezo1 在 ICH 后脑损伤中的作用及其机制。采用自体动脉血注入小鼠基底节的方法制备 ICH 模型。ICH 后，通过侧脑室注射给予 Piezo1 阻断剂 GsMTx4、Piezo1 激动剂 Yoda-1 或两者联合甘露醇，通过免疫印迹、水密性检测、伊文思蓝检测、尼氏染色、ELISA 等方法检测 Piezo1 水平及 Piezo1 在 ICH 后神经元损伤、脑水肿和神经功能障碍中的作用。结果显示，ICH 后 24 h ，体内（人和小鼠）和体外（在血红素处理的 HT22 细胞中，一种小鼠神经元细胞系）神经元中 Piezo1 蛋白水平明显上调。GsMTx4 治疗或与甘露醇联合治疗可显著下调 Piezo1 和 AQP4 水平，显著增加 Bcl2 水平，维持更多神经元存活，显著恢复脑血流，显著减轻脑水肿，显著降低血清 IL-6 水平，并几乎完全逆转 ICH 后 24 h 组小鼠的神经功能障碍。相反，Yoda-1 治疗则产生相反的效果。综上所述，Piezo1 在 ICH 后脑损伤的发病机制中起关键作用，可能成为 ICH 治疗的靶点。
