Effect of dexmedetomidine on hippocampal neuron apoptosis and the brain-derived neurotrophic factor/tyrosine kinase receptor B signaling pathway in epileptic rats
- VernacularTitle:右美托咪定对癫痫大鼠海马神经元凋亡及BDNF/TrκB信号通路的影响
- Author:
Li ZHAO
1
;
Cuicui FAN
1
Author Information
- Publication Type:Journal Article
- Keywords: Dexmedetomidine; Epilepsy; Brainderived neurotrophic factor; Tyrosine kinase receptor B; Neuronal apoptosis; Inflammatory response
- From: Journal of Apoplexy and Nervous Diseases 2023;40(9):813-818
- CountryChina
- Language:Chinese
- 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.
- Full text:2024061415382964147右美托咪定对癫痫大鼠海马神经元凋亡及BDNF_TrκB信号通路的影响.pdf
