自噬
创伤性脑损伤
神经保护
小胶质细胞
尼氏体
丙戊酸
细胞凋亡
生物
程序性细胞死亡
细胞生物学
神经科学
药理学
医学
病理
癫痫
炎症
免疫学
染色
生物化学
精神科
作者
Zhilong Zheng,Yanqing Wu,Zhengmao Li,Luxia Ye,Qi Lu,Yajiao Zhou,Yuan Yuan,Ting Jiang,Ling Xie,Yanlong Liu,Daqing Chen,Junming Ye,Wutigri Nimlamool,Hongyu Zhang,Jian Xiao
摘要
Abstract In recent years, many studies have focused on autophagy, an evolutionarily conserved mechanism that relies on lysosomes to achieve cellular metabolic requirements and organelle turnover, and revealed its important role in animal models of traumatic injury. Autophagy is a double‐edged sword. Appropriate levels of autophagy can promote the removal of abnormal proteins or damaged organelles, while hyperactivated autophagy can induce autophagic apoptosis. However, recent studies suggest that autophagic flux seems to be blocked after traumatic brain injury (TBI), which contributes to the apoptosis of brain cells. In this study, valproic acid (VPA), which was clinically used for epilepsy treatment, was used to treat TBI. The Morris water maze test, hematoxylin & eosin staining and Nissl staining were first conducted to confirm that VPA treatment had a therapeutic effect on mice after TBI. Western blotting, enzyme‐linked immunosorbent assay and immunofluorescence staining were then performed to reveal that VPA treatment reversed TBI‐induced blockade of autophagic flux, which was accompanied by a reduced inflammatory response. In addition, the variations in activation and phenotypic polarization of microglia were observed after VPA treatment. Nevertheless, the use of the autophagy inhibitor 3‐methyladenine partially abolished VPA‐induced neuroprotection and the regulation of microglial function after TBI, resulting in the deterioration of the central nervous system microenvironment and neurological function. Collectively, VPA treatment reversed the TBI‐induced blockade of autophagic flux in the mouse brain cortex, subsequently inhibiting brain cell apoptosis and affecting microglial function to achieve the promotion of functional recovery in mice after TBI. image Cover Image for this issue: doi: 10.1111/jnc.14755 .
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