Zhang Zhong-Hua, Zhou Xiao-Ming, Zhang Xin
Department of Neurosurgery, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing 210000, China.
Department of Anesthesiology, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing 210000, China.
Brain Sci. 2023 May 18;13(5):816. doi: 10.3390/brainsci13050816.
Clinically, early brain injury (EBI), which refers to the acute injuries to the whole brain in the phase of the first 72 h following subarachnoid hemorrhage (SAH), is intensely investigated to improve neurological and psychological function. Additionally, it will be meaningful to explore new therapeutic approaches for EBI treatment to improve the prognosis of patients with SAH. To investigate the underlying neuroprotection mechanism in vitro, the Protein tyrosine phosphatase 1B inhibitor (PTP1B-IN-1) was put in primary neurons induced by OxyHb to observe neuroapoptosis, neuroinflammation, and ER stress. Then, one hundred forty male mice were subjected to Experiment two and Experiment three. The mice in the SAH24h + PTP1B-IN-1 group were given an intraperitoneal injection of 5 mg/kg PTP1B-IN-1 30 min before anesthesia. SAH grade, neurological score, brain water content, Western blot, PCR, and Transmission Electron Microscopy (TEM) were performed to observe the underlying neuroprotection mechanism in vivo. Overall, this study suggests that PTP1B-IN-1 could ameliorate neuroapoptosis, neuroinflammation, and ER stress in vitro and in vivo by regulating the IRS-2/AKT signaling pathway, suggesting that PTP1B-IN-1 may be a candidate drug for the treatment of early brain injury after SAH.
临床上，早期脑损伤（EBI）是指蛛网膜下腔出血（SAH）后最初72小时内全脑的急性损伤，目前正受到深入研究以改善神经和心理功能。此外，探索治疗EBI的新方法以改善SAH患者的预后具有重要意义。为了在体外研究潜在的神经保护机制，将蛋白酪氨酸磷酸酶1B抑制剂（PTP1B-IN-1）作用于氧合血红蛋白（OxyHb）诱导的原代神经元，以观察神经细胞凋亡、神经炎症和内质网应激。然后，140只雄性小鼠接受实验二和实验三。SAH24h + PTP1B-IN-1组的小鼠在麻醉前30分钟腹腔注射5 mg/kg PTP1B-IN-1。通过SAH分级、神经功能评分、脑含水量、蛋白质印迹法、聚合酶链反应（PCR）和透射电子显微镜（TEM）观察体内潜在的神经保护机制。总体而言，本研究表明，PTP1B-IN-1可通过调节IRS-2/AKT信号通路改善体外和体内的神经细胞凋亡、神经炎症和内质网应激，提示PTP1B-IN-1可能是治疗SAH后早期脑损伤的候选药物。
