Dexmedetomidine protects neurons from kainic acid-induced excitotoxicity by activating BDNF signaling

Glutamatergic excitotoxicity is crucial in the pathogenesis of epileptic seizures. Dexmedetomidine, a potent and highly selective α2 adrenoceptor agonist, inhibits glutamate release from nerve terminals in rat cerebrocortical nerve terminals. However, the ability of dexmedetomidine to affect glutamate-induced brain injury is still unknown. Therefore, the present study evaluated the protective effect of dexmedetomidine against brain damage by using a kainic acid (KA) rat model, a frequently used model for temporal lobe epilepsy. Rats were treated with dexmedetomidine (1 or 5 μg/kg, intraperitoneally) 30 min before the KA (15 mg/kg) intraperitoneal injection. KA-induced seizure score and elevations of glutamate release in rat hippocampi were inhibited by pretreatment with dexmedetomidine. Histopathological and TUNEL staining analyzes showed that dexmedetomidine attenuated KA-induced neuronal death in the hippocampus. Dexmedetomidine ameliorated KA-induced apoptosis, and this neuroprotective effect was accompanied by inhibited the KA-induced caspase-3 expression as well as MAPKs phosphorylation, and reversed Bcl-2 down-expression, coupled with increased Nrf2, BDNF and TrkB expression in KA-treated rats. The results suggest that dexmedetomidine protected rat brains from KA-induced excitotoxic damage by reducing glutamate levels, suppressing caspase-3 activation and MAPKs phosphorylation, and enhancing Bcl-2, Nrf2, BDNF and TrkB expression in the hippocampus. Therefore, dexmedetomidine may be beneficial for preventing or treating brain disorders associated with excitotoxic neuronal damage. In conclusion, these data suggest that dexmedetomidine has the therapeutic potential for treating epilepsy. •Dexmedetomidine has considerable neuroprotective effect on KA-induced seizures in rats.•This protective effect is mediated by activating BDNF/TrkB pathway, inhibiting apoptosis and lowering glutamate levels.•Dexmedetomidine may be beneficial for preventing or treating brain disorders associated with excitotoxic neuronal damage.•Dexmedetomidine has the therapeutic potential for treating epilepsy.