Dexmedetomidine alleviates hippocampal neuronal damage in epilepsy through BDNF/TrkB pathway by inhibiting MeCP2

Epilepsy (EP) is a prevalent neurological disorder. The study sought to investigate the impact of dexmedetomidine (DEX) on hippocampal neuron damage, methyl-CpG binding protein 2 (MeCP2) expression, and brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (TrkB) pathway in EP in vitro model. The study involved the isolation of hippocampal neurons from newborn neonatal rats, which were identified utilizing microscopic observation and immunofluorescence staining. The EP in vitro model was developed using magnesium-free treatment. Next, the neurons were treated with 0, 1, 10, 100, and 200 μM DEX to investigate its impact on EP. Neuron viability and apoptosis were assessed using CCK-8, western blotting, and TUNEL assay. The levels of IL-6 and TNF-α were measured using ELISA. The determination of ROS and MDA levels and SOD activity was conducted to evaluate oxidative stress. Moreover, the binding of MeCP2 to the BDNF promoter was confirmed using a ChIP assay. The hippocampal neurons were successfully extracted from newborn neonatal rats. DEX of 100 and 200 μM significantly promoted neuronal viability and inhibited neuronal apoptosis, inflammation, oxidative stress, and MeCP2 expression induced by magnesium-free. MeCP2 inhibited the expression of BDNF/TrkB pathway by binding to the BDNF promoter. Moreover, MeCP2 silencing promoted neuronal viability and inhibited apoptosis, inflammation, and oxidative stress, while BNDF silencing restored it. Furthermore, DEX alleviated hippocampal neuronal damage. However, MeCP2 overexpression restored it. DEX alleviated hippocampal neuronal damage in EP through BDNF/TrkB pathway by down-regulating MeCP2 expression. DEX might be one of novel and effective anti-seizure medications.