Exploring the Role of Alpha Lipoic Acid in the Treatment of Traumatic Brain Injury: Pathways and Perspectives.

BACKGROUND: Traumatic brain injury (TBI) is known to be a critical health challenge with a significant number of hospital admissions. In addition to the primary injury and its complications, the secondary phase of the injury also causes numerous health issues. Neuroinflammation, oxidative stress (OS), and neuronal cell death are among the main outcomes of secondary injury. Although so far there are no drugs approved by the Food and Drug Administration for TBI's pharmacological treatment, numerous pharmaceutical compounds have been studied to help patients. Alpha lipoic acid (ALA), as a potent antioxidant agent, has been investigated for a considerable period. METHODS: Eligible original studies written in English on the effects of ALA in TBI were collected from PubMed, Embase, Scopus, Web of Science, and Google Scholar for clinical, in vivo, and in vitro studies. RESULTS: ALA is able to enter the blood-brain barrier due to its distinctive combination of hydrophilic and hydrophobic characteristics, enabling it to directly affect brain regions. It acts as a cofactor for enzymes in mitochondria, helping in oxidative carboxylation and replenishing other antioxidants like glutathione. This improves the glutathione/glutathione disulfide ratio during cellular stress, hence reducing cell death. In addition, ALA regulates oxidative, inflammatory, and apoptotic pathways by controlling the activity of caspase 3, caspase 9, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and inflammatory proteins, including tumor necrosis factor and inducible nitric oxide synthase. These methods highlight the potential of ALA in decreasing neuronal damage and OS in brain-related illnesses, including TBI. CONCLUSIONS: Based on this review, it can be concluded that ALA can potentially be administered as a therapeutic option for patients with TBI. However, more studies and trials are required to adjust the optimum dosing of ALA for the treatment of patients.