Fei-Sun Yi, Huang Miao, Qin Hao-Yue, Campos de SouzaHan Senio, Xue Han, Wang Yu-Ying, Wang Yi-Bo
Institute of Neurological Disease, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital Sichuan University Chengdu Sichuan China.
Center for Epigenetics and Induced Pluripotent Stem Cells, Kennedy Krieger Institute Johns Hopkins University Baltimore USA.
Ibrain. 2022 Dec 3;8(4):500-515. doi: 10.1002/ibra.12081. eCollection 2022 Winter.
Hypoxic-ischemic encephalopathy (HIE) is an important cause of neonatal death and disability, which can lead to long-term neurological and motor dysfunction. Currently, inhalation anesthetics are widely used in surgery, and some studies have found that isoflurane (ISO) may have a positive effect on neuroprotection. In this paper, we investigated whether ISO pretreatment has a neuroprotective effect on the neurological function of HIE rats. Here, 7-day-old neonatal rats were randomly divided into a sham group, a hypoxic-ischemic (HI) group, and an ISO pretreatment (pretreatment) group. The pretreatment group was pretreated with 2% ISO for 1 h, followed by the HI group to establish an HI animal model. The HI‑induced neurological injury was evaluated by Zea‑Longa scores and triphenyltetrazolium (TTC) staining. Neuronal number and histomorphological changes were observed with Nissl staining and Hematoxylin-eosin (HE) staining. In addition, motor learning memory function was evaluated by the Morris water maze (MWM), the Y-maze, and the rotarod tests. HI induced severe neurological dysfunction, brain infarction, and cell apoptosis as well as obvious neuron loss in neonatal rats. In the MWM, the rats in the pretreatment group showed a decrease in escape latency ( = 0.042), indicating that pretreatment with ISO could improve the learning ability of HI rats. The results of Nissl staining showed that in the HI group, there was an irregular arrangement of neurons and nuclear fixation; however, the cell damage was significantly reduced and the total number of neurons was increased after ISO pretreatment ( < 0.001). In conclusion, ISO pretreatment improved cognitive function and attenuated HI-induced reduction of Nissl-positive cells and spatial memory impairment, suggesting that pretreatment with ISO before HI modeling could reduce neuronal cell death in the hippocampus after HI.
缺氧缺血性脑病（HIE）是新生儿死亡和残疾的重要原因，可导致长期神经和运动功能障碍。目前，吸入麻醉剂在手术中广泛使用，一些研究发现异氟烷（ISO）可能具有神经保护作用。在本文中，我们研究了ISO预处理对HIE大鼠神经功能是否具有神经保护作用。在此，将7日龄新生大鼠随机分为假手术组、缺氧缺血（HI）组和ISO预处理组。预处理组用2% ISO预处理1小时，随后与HI组一起建立HI动物模型。通过Zea-Longa评分和三苯基四氮唑（TTC）染色评估HI诱导的神经损伤。用尼氏染色和苏木精-伊红（HE）染色观察神经元数量和组织形态学变化。此外，通过莫里斯水迷宫（MWM）、Y迷宫和转棒试验评估运动学习记忆功能。HI诱导新生大鼠出现严重的神经功能障碍、脑梗死、细胞凋亡以及明显的神经元丢失。在MWM试验中，预处理组大鼠的逃避潜伏期缩短（P = 0.042），表明ISO预处理可提高HI大鼠的学习能力。尼氏染色结果显示，HI组神经元排列不规则且核固缩；然而，ISO预处理后细胞损伤明显减轻，神经元总数增加（P < 0.001）。总之，ISO预处理改善了认知功能，减轻了HI诱导的尼氏阳性细胞减少和空间记忆损害，表明在HI建模前用ISO预处理可减少HI后海马神经元细胞死亡。
