Che Ji, Wu Yuanyuan, Dong Jing, Jiang Xuliang, Yang Li, Chen Yali, Zhang Jun
Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China.
Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China.
Exp Neurol. 2025 Mar;385:115086. doi: 10.1016/j.expneurol.2024.115086. Epub 2024 Dec 3.
Inhalational anesthetic sevoflurane can cause myelination damage in developing brain. This study examines the effects of histamine receptor 3 (H3) antagonist thioperamide on sevoflurane-induced hypomyelination and neurobehavioral deficits.
Neonatal C57BL/6 mice were exposed to sevoflurane for consecutive three days and treated with H3 receptor antagonist thioperamide. Myelination was assessed in the hippocampus and corpus callosum. The neurobehavioral functions were also examined. Primary oligodendrocyte progenitor cells (OPCs) were used for in vitro experiments and the underlying mechanism.
Inhibition of H3 receptor with thioperamide significantly alleviated sevoflurane-induced impairments in myelination and neurobehavioral functions. In vitro experiments showed that thioperamide reversed the effects of sevoflurane on OPCs migration, proliferation and differentiation into mature oligodendrocytes. Mechanistically, thioperamide improved sevoflurane-induced hypomyelination may through H3 receptor-mediated GSK-3β/β-catenin pathway.
H3 receptor antogonist thioperamide could protect developing brain against hypomyelination and neurobehavioral deficits after repeated sevoflurane exposure. Therefore H3 receptor is a potential target for preventing anesthetic-induced developmental neurotoxicity.
吸入性麻醉药七氟醚可导致发育中的大脑出现髓鞘形成损伤。本研究探讨组胺受体3（H3）拮抗剂硫代酰胺对七氟醚诱导的髓鞘形成不足和神经行为缺陷的影响。
将新生C57BL/6小鼠连续三天暴露于七氟醚中，并给予H3受体拮抗剂硫代酰胺治疗。评估海马体和胼胝体中的髓鞘形成情况。还检测了神经行为功能。原代少突胶质前体细胞（OPCs）用于体外实验及探究潜在机制。
硫代酰胺抑制H3受体可显著减轻七氟醚诱导的髓鞘形成和神经行为功能损伤。体外实验表明，硫代酰胺可逆转七氟醚对OPCs迁移、增殖及分化为成熟少突胶质细胞 的影响。机制上，硫代酰胺改善七氟醚诱导的髓鞘形成不足可能是通过H3受体介导的GSK-3β/β-连环蛋白通路。
H3受体拮抗剂硫代酰胺可保护发育中的大脑免受反复暴露于七氟醚后出现的髓鞘形成不足和神经行为缺陷的影响。因此，H3受体是预防麻醉药诱导的发育性神经毒性的一个潜在靶点。
