Alpha lipoic acid inhibits neural apoptosis via a mitochondrial pathway in rats following traumatic brain injury

Alpha lipoic acid (ALA) is a powerful antioxidant that has proven protective effects against brain damage following a traumatic brain injury (TBI) in rats. However, the molecular mechanisms underlying these effects are not well understood. This study investigated the effect of ALA on neural apoptosis and the potential mechanism of these effects in the weight-drop model of TBI in male Sprague-Dawley rats that were treated with ALA (20 or 100 mg/kg) or vehicle via intragastric administration 30 min after TBI. Brain samples were collected 48 h later for analysis. ALA treatment resulted in a downregulation of caspase-3 expression, reduced the number of positive cells in the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and improved neuronal survival. Furthermore, the level of malondialdehyde and glutathione peroxidase activity were restored, while Bcl-2-associated X protein translocation to mitochondria and cytochrome c release into the cytosol were reduced by ALA treatment. These results demonstrate that ALA improves neurological outcome in rats by protecting neural cell against apoptosis via a mechanism that involves the mitochondria following TBI. (C) 2015 Elsevier Ltd. All rights reserved.