Protective effect of isoflurane preconditioning on neurological function in rats with HIE

Yi Fei-Sun; Miao Huang; Hao-Yue Qin; Senio Campos de SouzaHan; Han Xue; Yu-Ying Wang; Yi-Bo Wang

doi:10.1002/ibra.12081

Protective effect of isoflurane preconditioning on neurological function in rats with HIE

Ibrain. 2022 Dec 3;8(4):500-515. doi: 10.1002/ibra.12081. eCollection 2022 Winter.

Authors

Yi Fei-Sun^{1

2}, Miao Huang³, Hao-Yue Qin³, Senio Campos de SouzaHan⁴, Han Xue⁵, Yu-Ying Wang⁵, Yi-Bo Wang⁵

Affiliations

¹ Institute of Neurological Disease, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital Sichuan University Chengdu Sichuan China.
² Center for Epigenetics and Induced Pluripotent Stem Cells, Kennedy Krieger Institute Johns Hopkins University Baltimore USA.
³ Department of Anesthesiology Southwest Medical University Luzhou Sichuan China.
⁴ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences University of Macau Macau SAR China.
⁵ School of Basic Medical Sciences Jinzhou Medical University Jinzhou Liaoning China.

Abstract

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 (p = 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 (p < 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.

Keywords: Isoflurane; anesthesia; brain protection; hypoxic–ischemic encephalopathy; preconditioning.