Hypoxic ischemic encephalopathy (HIE) is an important cause of neonatal death and disability, which can lead to long-term neurological and motor dysfunction. At present, the treatment mainly focuses on the symptomatic treatment in the acute phase and rehabilitation after injury, but the effect is not satisfactory, and more effective methods are urgently needed. Due to the widespread use of inhalation anesthetics in surgery, it has been found that iso urane (ISO) preconditioning may have a positive effect on neuroprotection. The aim of this study was to investigate the effects of ISO preconditioning on neurological function and behavior in HIE rats. MethodsNeonatal rats were used to create hypoxic-ischemic (HI) model by ligating the right common carotid artery at 7 days and then in a hypoxia chamber. The effects of anesthetic drugs on neurological function after one hour of ISO preconditioning were assessed after modeling by Morris water maze(MWM), Ymaze, and rotarod tests at one month. Thereafter, samples were taken at 1 and 42 days for Nissl staining and Hematoxylin-Eosin (HE) staining to observe neuronal number and histomorphology changes. The relationship of behaviour and morphology tests were measured. ResultsIschemia and hypoxia could induce neuronal injury, neurological dysfunction and severe long-term motor function injury. Histological staining and behavioural evaluations were performed to elucidate the pathological changes and neurobehavioural variation after ISO treatment. We found ISO administration signi cantly reduced the infarct volume of brain tissues and improved the autonomous activities of neonatal rats, ISO preconditioning signi cantly reduced neuronal apoptosis induced by HI, reduced cerebral infarction volume, improved histopathological damage of nerve cells, improved long-term cognitive function, and attenuated HI-induced Nissl total cells to reduce and reduce long-term spatial memory impairment caused by hypoxia-ischemia during the maturation of injured brain. ConclusionISO preconditioning can protect the brain injury and promote the recovery of neurological function in neonatal rats with HIE, which may be through inhibiting the neuronal cell death in the cortex and hippocampus after HI.