Midazolam, a widely used anesthetic, inhibits proliferation of neural stem cells (NSCs) and induces neuroapoptosis in neonates. Dexmedetomidine, an effective auxiliary medicine in clinical anesthesia, protects the developing brain against volatile anesthetic-induced neuroapoptosis. Whether dexmedetomidine protects against neurogenesis damage induced by midazolam remains unknown. This study aims to clarify the protective effect of dexmedetomidine on midazolam-induced neurogenesis damage and explore its potential mechanism. Postnatal 7-day-old Sprague-Dawley (SD) rats and cultured NSCs were treated with either normal saline, midazolam, or dexmedetomidine combined with midazolam. The rats were sacrificed at 1, 3, and 7 days after treatment. Cell proliferation was assessed by 5-bromodeoxyurdine (BrdU) incorporation. Cell viability was determined using MTT assay. Cell differentiation and apoptosis were detected by immunofluorescent staining and terminal dUTP nick-end labeling (TUNEL), respectively. The protein levels of p-JNK, p-P38, and cleaved caspase-3 were quantified using Western blotting. Midazolam decreased cell proliferation and increased cell apoptosis in the subventricular zone (SVZ), the subgranular zone (SGZ) of the hippocampus, and cultured NSCs. Moreover, midazolam decreased cell viability and increased the expression of p-JNK and p-P38 in cultured NSCs. Co-treatment with dexmedetomidine attenuated midazolam-induced changes in cell proliferation, viability, apoptosis, and protein expression of p-JNK and p-P38 in cultured NSCs. Midazolam and dexmedetomidine did not affect the differentiation of the cultured NSCs. These results indicate that dexmedetomidine alleviated midazolam-induced neurogenesis damage via JNK and P38 MAPK pathways.

中文翻译：

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右美托咪定通过JNK和P38 MAPK途径减轻新生鼠咪达唑仑暴露后的神经发生损害。

咪达唑仑是一种广泛使用的麻醉剂，可抑制神经干细胞（NSC）的增殖并诱导新生儿的神经细胞凋亡。右美托咪定是临床麻醉中的有效辅助药物，可保护发育中的大脑免受挥发性麻醉药诱导的神经细胞凋亡的影响。右美托咪定是否能预防由咪达唑仑引起的神经发生损害尚不清楚。本研究旨在阐明右美托咪定对咪达唑仑诱导的神经发生损伤的保护作用，并探讨其潜在机制。产后7天大的Sprague-Dawley（SD）大鼠和培养的NSC用生理盐水，咪达唑仑或右美托咪定联合咪达唑仑治疗。在处理后第1、3和7天处死大鼠。通过5-溴脱氧尿嘧啶（BrdU）掺入评估细胞增殖。使用MTT测定法测定细胞活力。分别通过免疫荧光染色和末端dUTP缺口末端标记（TUNEL）检测细胞分化和凋亡。使用蛋白质印迹法定量测定p-JNK，p-P38和裂解的caspase-3的蛋白水平。咪达唑仑减少了海马的脑室下区（SVZ），颗粒下区（SGZ）和培养的神经干细胞的细胞增殖并增加了细胞凋亡。此外，咪达唑仑在培养的神经干细胞中降低细胞活力并增加p-JNK和p-P38的表达。与右美托咪定的共同处理减弱了咪达唑仑诱导的培养的NSC细胞增殖，活力，凋亡和p-JNK和p-P38蛋白表达的变化。咪达唑仑和右美托咪定不影响培养的神经干细胞的分化。