Dexmedetomidine Attenuates Neuroinflammatory-Induced Apoptosis after Traumatic Brain Injury via Nrf2 signaling pathway

Objective Dexmedetomidine (DEX) exhibits neuroprotective effects as a multifunctional neuroprotective agent in numerous neurological disorders. However, in traumatic brain injury (TBI), the molecular mechanisms of these neuroprotective effects remain unclear. The present study investigated whether DEX, which has been reported to exert protective effects against TBI, could attenuate neuroinflammatory-induced apoptosis and clarified the underlying mechanisms. Methods A weight-drop model was established, and DEX was intraperitoneally injected 30 min after inducing TBI in rats. The water content in the brain tissue was measured. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays were performed on histopathological tissue sections to evaluate neuronal apoptosis. Enzyme-linked immunosorbent assay and PCR were applied to detect the levels of the inflammatory factors, TNF-alpha, IL-1 beta, IL-6, and NF-kappa B. Results TBI-challenged rats exhibited significant neuronal apoptosis, which was characterized via the wet-to-dry weight ratio, neurobehavioral functions, TUNEL assay results and the levels of cleaved caspase-3, Bax upregulation and Bcl-2, which were attenuated by DEX. Western blot, immunohistochemistry, and PCR results revealed that DEX promoted Nrf2 expression and upregulated expression of the Nrf2 downstream factors, HO-1 and NQO-1. Furthermore, DEX treatment markedly prevented the downregulation of inflammatory response factors, TNF-alpha, IL-1 beta and NF-kappa B, and IL-6. Interpretation Administering DEX attenuated inflammation-induced brain injury in a TBI model, potentially via the Nrf2 signaling pathway.