Zeng Shuang, Zhu Ruilou, Wang Yangyang, Yang Yitian, Li Ningning, Fu Ningning, Sun Mingyang, Zhang Jiaqiang
Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
Academy of Medical Sciences of Zhengzhou University, Zhengzhou, China.
Front Cell Neurosci. 2022 Sep 13;16:964227. doi: 10.3389/fncel.2022.964227. eCollection 2022.
In neonatal mice, anesthesia with sevoflurane depolarizes the GABA Type A receptor (GABAR), which leads to cognitive impairment. Calcium accumulation in neurons can lead to neurotoxicity. Voltage-gated calcium channels (VGCCs) can increase intracellular calcium concentration under isoflurane and hypoxic conditions. The underlying mechanisms remain largely unknown.
Six-day-old mice were anesthetized with 3% sevoflurane for 2 h/day for 3 days. The Y-Maze, new object recognition (NOR) test, the Barnes maze test, immunoassay, immunoblotting, the TUNEL test, and Golgi-Cox staining were used to assess cognition, calcium concentration, inflammatory response, GABAR activation, VGCC expression, apoptosis, and proliferation of hippocampal nerve cells in mice and HT22 cells.
Compared with the control group, mice in the sevoflurane group had impaired cognitive function. In the sevoflurane group, the expression of Gabrb3 and Cav1.2 in the hippocampal neurons increased ( < 0.01), the concentration of calcium ions increased ( < 0.01), inflammatory reaction and apoptosis of neurons increased ( < 0.01), the proliferation of neurons in the DG area decreased ( < 0.01), and dendritic spine density decreased ( < 0.05). However, the inhibition of Gabrb3 and Cav1.2 alleviated cognitive impairment and reduced neurotoxicity.
Sevoflurane activates VGCCs by inducing GABAR depolarization, resulting in cognitive impairment. Activated VGCCs cause an increase in intracellular calcium concentration and an inflammatory response, resulting in neurotoxicity and cognitive impairment.
在新生小鼠中，七氟醚麻醉会使γ-氨基丁酸A型受体（GABAR）去极化，从而导致认知障碍。神经元中的钙积累可导致神经毒性。在异氟醚和缺氧条件下，电压门控钙通道（VGCCs）可增加细胞内钙浓度。其潜在机制在很大程度上仍不清楚。
对6日龄小鼠用3%七氟醚麻醉，每天2小时，共3天。采用Y迷宫、新物体识别（NOR）试验、巴恩斯迷宫试验、免疫测定、免疫印迹、TUNEL试验和高尔基-考克斯染色来评估小鼠和HT22细胞中海马神经细胞的认知、钙浓度、炎症反应、GABAR激活、VGCC表达、凋亡和增殖情况。
与对照组相比，七氟醚组小鼠的认知功能受损。在七氟醚组中，海马神经元中Gabrb3和Cav1.2的表达增加（<0.01），钙离子浓度增加（<0.01），神经元的炎症反应和凋亡增加（<0.01），齿状回区域神经元的增殖减少（<0.01），树突棘密度降低（<0.05）。然而，抑制Gabrb3和Cav1.2可减轻认知障碍并降低神经毒性。
七氟醚通过诱导GABAR去极化激活VGCCs，导致认知障碍。激活的VGCCs导致细胞内钙浓度增加和炎症反应，从而导致神经毒性和认知障碍。
