Dexmedetomidine Exerts A Cerebroprotective Effect In Neonatal Rats With Hypoxic-ischemic Encephalopathy By Promoting Cerebral Angiogenesis

Objective:Neonatal hypoxic-ischemic encephalopathy(HIE),a severe disease due to perinatal hypoxic asphyxia and one of the leading causes of acute neonatal death,has attracted much attention.After HIE initiates neurological dysfunction,cerebral angiogenesis is an important process for brain injury repair.Numerous studies have shown that dexmedetomidine(DEX)exerts certain cerebroprotective effects through various mechanisms,but there has been no literature directly elucidating the effects of DEX on cerebral angiogenesis.Therefore,in this study,we established a neonatal rat model of HIE to explore whether DEX exerts a cerebroprotective effect by promoting cerebral angiogenesis.Methods:1.Experimental grouping and model preparation: the 7-day-old rats were randomly divided into five groups: sham group(Group S),hypoxia ischemia group(Group HIE),low-dose DEX group(Group D10),medium-dose DEX group(Group D50)and high-dose DEX group(Group D100).The sham group was treated with surgery only,while the HIE model was prepared by ligating the left common carotid artery and hypoxia to form the group HIE,and the low-dose、medium-dose and high-dose DEX groups were intraperitoneally injected with dexmedetomidine 10μg/kg、50μg / kg and100μg/kg respectively.2.Hypoxic ischemic brain injury observation: the neurobehavioral scores of rats were performed 24 h after modeling,the cerebral infarct volumes were determined by TTC staining 48 h after operation,and the open field test was performed 35 days after operation.3.Observation of cerebral angiogenesis: the VEGF protein expression level in cerebral cortex was measured at 48 h after modeling operation;The diameters of the arterial circle of Willis and basilar artery were measured by carbon black perfusion 7 days after the operation.Results:1.Neurological deficit scores and righting behavior scores were not significantly different between groups.Compared with the group S,the rats in the group HIE had obvious cerebral infarction,and the volume of cerebral infarction in the rats of the group DEX was reduced.Compared with the group S,rats in the group HIE showed a decrease in the total travel distance in the open field test,and the total travel distance in the group DEX increased.2.Compared with the group S,the VEGF protein expression level in the cerebral cortex of rats of both the group HIE and the group DEX were increased.Compared with the group HIE,the VEGF protein expression level in the cerebral cortex of rats of the group DEX increased.There was no significant difference in the diameter of the arterial circle of Willis between the group HIE and the group S,and the diameter of the arterial circle of Willis was increased in the group DEX compared with the group HIE.The diameter of the basilar artery was increased in the group HIE compared with the group S,but the difference in basilar artery diameter between the group DEX and the group HIE was not statistically significant.Conclusions:1.Hypoxic ischemic injury can stimulate cerebral angiogenesis in neonatal rats to some extent,but it is not enough to improve the outcome of cerebral infarction and impaired exercise capacity in neonatal rats with HIE.2.DEX can significantly reduce the cerebral infarct volume and promote the recovery of exercise capacity in neonatal rats with HIE.3.DEX can alleviate brain injury and exert a cerebroprotective effect by promoting cerebral angiogenesis in neonatal rats with HIE.