2. Academic Validation
  3. Roles of mechanosensitive ion channel PIEZO1 in the pathogenesis of brain injury after experimental intracerebral hemorrhage

Roles of mechanosensitive ion channel PIEZO1 in the pathogenesis of brain injury after experimental intracerebral hemorrhage

  • Neuropharmacology. 2024 Mar 13:109896. doi: 10.1016/j.neuropharm.2024.109896.
Min Qi 1,  Ran Liu 2,  Fan Zhang 3,  Zhipeng Yao 3,  Meng-Liang Zhou 4,  Xiaochun Jiang 5,  Shizhang Ling 6
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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; School of Chemistry and Chemical Engineering & Interdisciplinary Innovation Institute for Medicine and Engineering, Southeast University, Nanjing, 211189, China.
  • 4 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; Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, China.
  • 5 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. Electronic address: jiangxiaochun2019@hotmail.com.
  • 6 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. Electronic address: sling@wnmc.edu.cn.
PMID: 38490299 DOI: 10.1016/j.neuropharm.2024.109896
Abstract

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.

Keywords

Brain injury; Intracerebral hemorrhage; Ion channel; Piezo 1.

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