Valproic acid affects neuronal fate and microglial function via enhancing autophagic flux in mice after traumatic brain injury

AbstractIn 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 contr ibutes to the apoptosis of brain cells. In our current study, valproic acid (VPA), which was clinically used for epilepsy treatment, was used to treat TBI. The Morris water maze test, hematoxylin& eosin (H&E) 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 (ELISA) 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 o f microglia were observed after VPA treatment. Nevertheless, the use of the autophagy inhibitor 3‐methyladenine (3‐MA) partially abolished VPA‐induced neuroprotection and the regulation of microglial function after TBI, resulting in the deteriorati...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research