CTL-Derived Granzyme B Participates in Hippocampal Neuronal Apoptosis Induced by Cardiac Arrest and Resuscitation in Rats
CTL-Derived Granzyme B Participates in Hippocampal Neuronal Apoptosis Induced by Cardiac Arrest and Resuscitation in Rats
复制标题
CTL 衍生的颗粒酶 B 参与大鼠心脏骤停和复苏诱导的海马神经元凋亡
DOI：
10.3389/fneur.2019.01306
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发表时间：
2019-12-12
影响因子：
3.4
通讯作者：
Zhang, Yong-Mei
中科院分区：
文献类型：
--
作者：
Ji, Ning-Ning;Wu, Liang;Zhang, Yong-Mei
Hippocampal neuronal apoptosis is a devastating consequence of cardiac arrest (CA) and subsequent cardiopulmonary resuscitation (CPR). In this study, we assessed the contribution of cytotoxic T lymphocyte (CTL)-derived toxic mediator granzyme B (Gra-b) to the hippocampal neuronal apoptosis following CA/CPR in rats. Rats that experienced CA/CPA presented with cytosomal shrinkage, dense cytoplasm, and intensive eosinophilic staining in the CA1 region of dorsal hippocampus. CA/CPR rats also exhibited inability in spatial navigation and a local infiltration of peripheral CD8+ T cells into the hippocampus. The protein levels of Gra-b, cleaved Caspase-3, and cleaved PARP1 were significantly elevated in rats undergoing CA/CPR. Pretreatment with Gra-b inhibitor suppressed Gra-b release, attenuated hippocampal neuronal apoptosis, as well as improved cognitive impairment. Together, this study indicates that CTL-derived Gra-b is involved in the CA/CPR-induced neuronal apoptosis, and pharmacological manipulation of Gra-b may represent a novel avenue for the treatment of brain injury following CA/CPR.
