Tetrahydrocurcumin provides neuroprotection in rats after traumatic brain injury: autophagy and the PI3K/AKT pathways as a potential mechanism

BackgroundTetrahydrocurcumin provides neuroprotection in multiple neurologic disorders by modulating oxidative stress, inflammatory responses, and autophagy. However, in traumatic brain injury (TBI), it is unclear whether a beneficial effect of tetrahydrocurcumin exists. In this study, we hypothesized that administration of tetrahydrocurcumin provides neuroprotection in a rat model of TBI.Material and methodsBehavioral studies were performed by recording and analyzing beam-walking scores. The role of tetrahydrocurcumin on neurons death was assessed via Nissl staining. We then performed Western blot analyses, terminal deoxynucleotidyl transferase 2'-deoxyuridine-5'-triphosphate (dUTP) nick end labeling assays and immunofluorescence staining to evaluate autophagy and apoptosis. Phospho-protein kinase B (p-AKT) was also assessed via Western blotting.ResultsOur data indicated that administration of tetrahydrocurcumin alleviated brain edema, attenuated TBI-induced neuron cell death, decreased the degree of apoptosis and improved neurobehavioral function, which were accompanied by enhanced autophagy and phospho-AKT after TBI. Moreover, the autophagy inhibitor 3-methyladenine and the PI3K kinase inhibitor LY294002 partially reversed the neuroprotection of tetrahydrocurcumin after TBI.ConclusionsThis study indicates that tetrahydrocurcumin protects neurons from TBI-induced apoptotic neuronal death, which may be through modulation autophagy and PI3K/AKT pathways. Thus, tetrahydrocurcumin may be an attractive therapeutic agent for TBI.