Effect of dexmedetomidine on hippocampal neuron apoptosis and the brain-derived neurotrophic factor/tyrosine kinase receptor B signaling pathway in epileptic rats / 中风与神经疾病杂志

ABSTRACT

@#Objective To investigate the effect of dexmedetomidine on hippocampal neuron apoptosis and the brain­derived neurotrophic factor（BDNF）/tyrosine kinase receptor B（TrκB） signaling pathway in epileptic rats. Methods A rat model of epilepsy was established by intraperitoneal injection of lithium chloride，atropine sulfate，and pilocarpine hydrochloride. After successful modeling，36 rats were randomly divided into model group，dexmedetomidine（50 μg/kg） group，and dexmedetomidine（50 μg/kg）+LM22B-10（a BDNF/TrκB pathway activator，5 mg/kg） group，with 12 rats in each group，and another 12 rats were selected as control group. After modeling ended，the rats in each group were given corresponding drug intervention once a day for 1 week. At 24 hours after the end of administration，seizure frequency and duration were recorded for each group；TUNEL staining was used to observe hippocampal neuron apoptosis；immunofluorescent staining was used to observe β­tubulin Ⅲ（Tuj1）­positive cells in brain tissue of the hippocampal CA1 region；ELISA was used to measure the levels of tumor necrosis factor­α（TNF­α） and interleukin­6（IL­6） in brain tissue of the hippocampal CA1 region；Western blot was used to measure the protein expression levels of BDNF，TrκB，B­cell lymphoma­2 associated X protein（Bax），and B cell lymphoma­2（Bcl­2） in brain tissue of the hippocampal CA1 region. Results Compared with the control group，the model group had significant increases in seizure frequency and duration，the number of apoptotic hippocampal neurons，the levels of TNF­α and IL­6 in the hippocampal CA1 region，and the protein expression levels of BDNF，TrκB，and Bax in the hippocampal CA1 region（P<0.05） and significant reductions in the number of Tuj1­positive cells and the protein expression level of Bcl-2 in the hippocampal CA1 region（P<0.05）. Compared with the model group，the dexmedetomidine group had significant reductions in seizure frequency and duration，the number of apoptotic hippocampal neurons，the levels of TNF-α and IL­6 in the hippocampal CA1 region，and the protein expression levels of BDNF，TrκB，and Bax in the hippocampal CA1 region（P<0.05） and significant increases in the number of Tuj1­positive cells and the protein expression level of Bcl­2 in the hippocampal CA1 region（P<0.05）. LM22B­10 could partially reverse the role of dexmedetomidine in improving various indicators of epileptic rats（P<0.05）. Conclusion Dexmedetomidine can reduce seizure in epileptic rats，inhibit the apoptosis of hippocampal neurons，and alleviate inflammatory response in rats，possibly by inhibiting the activation of the BDNF/TkB signal pathway.