Protective effect of midazolam against convulsion in neonatal rats via down-regulation of LC3 and Beclin-1 expression

Abstract

Purpose: To investigate the effect of midazolam on growth of neurocytes in vitro and in neonatal rats. Methods: Neurocyte proliferation and activity of lactate dehydrogenase were assessed by MTT and lactate dehydrogenase assays, respectively. Western blotting was used to determine the effect of midazolam on LC3, Bax, p62 and Beclin-1 protein expressions. Results: The suppression of neurocyte proliferation byconvulsion was alleviated significantly (p < 0.05) by midazolum treatment. Exposure of convulsion model of neurocytes to midazolum suppressed LC3, Bax, p62 and Beclin-1 protein expression. Midazolum exposure of convulsion model of neurocytes suppressed LDH, caspase-3, caspase-8 and caspase-9 activities. The 3-MA (autophagy inhibitor) treatment also significantly (p < 0.05) promoted neurocyte viability after convulsion induction. In convulsion-induced neurocytes, 3-MA exposure suppressed expression of caspase-3/8/9, LC3, Bax, Beclin-1 and p62, while application of midazolum treatment to the rats with convulsion markedly decreased brain water content and neurocyte apoptosis (p < 0.05). Treatment with midazolum inhibited LC3, p62 and Beclin-1 expression in the rat model of convulsion. Conclusion: Midazolum promotes neurocyte proliferation and inhibits edema development via downregulation of autophagy. Therefore, midazolum can potentially be used for the treatment of convulsion, but further studies need to be carried out first. Keywords: Convulsion, Neurocytes, Caspase, Autophagy, Mitochondrial pathway