Multiple sevoflurane exposures may damage the developing brain. The neuroprotective function of dexmedetomidine has been widely confirmed in animal experiments and human studies. However, the effect of dexmedetomidine on the glymphatic system has not been clearly studied. We hypothesized that dexmedetomidine could alleviate sevoflurane-induced circulatory dysfunction of the glymphatic system in young mice. Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 2 h daily, continuously for 3 days. Intraperitoneal injection of either normal saline or dexmedetomidine was administered before every anaesthesia. Meanwhile the circulatory function of glymphatic system was detected by tracer injection at P8 and P32. On P30-P32, behavior tests including open field test, novel object recognition test, and Y-maze test were conducted. Primary astrocyte cultures were established and treated with the PI3K activator 740Y-P, dexmedetomidine, and small interfering RNA (siRNA) to silence ΔFosB. We propose for the first time that multiple exposure to sevoflurane induces circulatory dysfunction of the glymphatic system in young mice. Dexmedetomidine improves the circulatory capacity of the glymphatic system in young mice following repeated exposure to sevoflurane through the PI3K/AKT/ΔFosB/AQP4 signaling pathway, and enhances their long-term learning and working memory abilities.

多次接触七氟醚可能会损害发育中的大脑。右美托咪定的神经保护功能已在动物实验和人体研究中得到广泛证实。然而，右美托咪定对类淋巴系统的影响尚未明确研究。我们假设右美托咪定可以减轻七氟烷引起的幼鼠类淋巴系统循环功能障碍。六日龄的 C57BL/6 小鼠每天暴露于 3% 七氟醚 2 小时，连续 3 天。每次麻醉前腹腔注射生理盐水或右美托咪定。同时在P8、P32处注射示踪剂检测类淋巴系统循环功能。 P30-P32进行了行为测试，包括旷场测试、新物体识别测试、Y迷宫测试。建立原代星形胶质细胞培养物，并用 PI3K 激活剂 740Y-P、右美托咪定和小干扰 RNA (siRNA) 处理以沉默 ΔFosB。我们首次提出，多次暴露于七氟醚会导致幼鼠类淋巴系统循环功能障碍。右美托咪定通过 PI3K/AKT/ΔFosB/AQP4 信号通路改善反复接触七氟醚的幼鼠类淋巴系统循环能力，增强其长期学习和工作记忆能力。