基础和临床研究的证据表明临床上使用的全身麻药能导致发育期神经毒性，引发神经退行性病变以及认知功能障碍。神经元一直是全身麻药引起的神经毒性的研究焦点，然而，星状胶质细胞,人脑中数目最多的胶质细胞，在其中扮演的角色不为人知。本项目基于最新的科研进展，设立四个实验目标，多方面探讨七氟醚和地氟醚这两种在临床小儿麻醉中广泛使用的麻药对小鼠脑发育期的星状胶质细胞的基本细胞生物学的影响。本项目将采用先进的技术手段，包括细胞形态的重建、脑切片膜片钳电生理以及基于钙荧光蛋白探针的共聚焦钙成像等，探讨七氟醚和地氟醚引起的星状胶质细胞形态，胞外神经递质及钾离子平衡和钙信号三大功能障碍。我们还将记录麻醉药物引起的神经元基本功能障碍，结合星状胶质细胞上的实验数据提出基于星状胶质细胞的新机制。本项目的实验将证明对星状胶质功能障碍的早期干预或成为麻药引起的发育期神经毒性的治疗靶点。

Increasing preclinical and clinical evidence suggest that exposure to anesthetics in common clinical use may cause developmental neurotoxicity, triggering neurodegeneration and cognitive dysfunctions in children. Whereas neuron has taken center stage in anesthetic-induced developmental neurotoxicity (AIDN), roles of astrocytes, the most abundant glial cells in the brain, in AIDN remain largely unexplored. The current project with four specific aims builds logically on the recent advances, and seeks to explore broadly fundamental astrocytic cell biology in the context of sevoflurane or desflurane, two anesthetics widely used in pediatric anesthetic practice, induced neurotoxicity in developing mouse brain,. The project will employ state-of-the-art techniques including morphology reconstruction, patch clamp electrophysiology in brain slices, calcium imaging under confocal microscopy with genetically encoded calcium indicators (GECIs) to study astrocytic dysfunctions in morphology, extracellular neurotransmitter/K+ homeostasis and calcium signaling induced by sevoflurane or desflurane. Also, we will measure neuronal dysfunctions using electrophysiology to build astrocytic mechanisms underlying AIDN. We expect that our experiments would be proof-of-concept that early intervention of astrocyte dysfunctions may be exploited as therapeutic targets in AIDN.