| Background and objectionAs a common acute cerebrovascular disease,stroke is characterized by high incidence,high mortality,and high disability rate.With the aging of the Chinese population,the incidence of stroke continues to rise,which brings enormous economic burden to society and families.In addition,stroke is a serious complication during the perioperative period,which can significantly increase the surgical mortality and late mortality,and affect the postoperative recovery of patients.Restoration of blood flow as a key treatment for acute stroke,however,is usually accompanied by cerebral ischemia-reperfusion injury(CIRI),and there is currently a lack of effective treatment measures to reduce CIRI and improve prognosis.Many years of research have shown that various anesthetics have different degrees of neuroprotective effects.In recent years,esketamine has attracted widespread attention and application in the treatment of severe pain,prevention of opioid-induced hyperalgesia,antidepressant,antiepileptic,and other fields,due to its advantages of fast onset,strong analgesic and sedative effects,fast metabolism and elimination,and high controllability.Studies have shown that ketamine can reduce neuronal apoptosis and inhibit inflammatory reactions by suppressing NMDA receptor activation and excitotoxic amino acid signal transduction.Ketamine also plays a neuroprotective role by maintaining cerebral perfusion pressure through activation of the sympathetic nervous system.Conversely,some studies have suggested that ketamine has neurotoxic effects,which may impair memory,affect cognitive function,and even trigger psychiatric disorders such as schizophrenia.Therefore,the neuroprotective effects of ketamine remain controversial,and its impact on cerebral ischemia-reperfusion injury has been poorly studied.This study aims to investigate the effects of different doses of esketamine on cerebral ischemia-reperfusion injury.Oxidative stress is a key factor in the occurrence and development of CIRI,and inhibiting the oxidative stress response after cerebral ischemia-reperfusion is an important target for the treatment of CIRI.Numerous studies have shown that activation of the Nrf2/HO-1 signaling pathway can enhance cellular antioxidant stress capacity,alleviate the cascade reaction of inflammation,apoptosis,and injury caused by oxidative damage,and play a significant role in reducing ischemia-reperfusion injury(IRI).Therefore,this study aims to further investigate whether esketamine can reduce stress injury by suppressing oxidative stress response,and whether the Nrf2/HO-1 signaling pathway is involved in this regulatory process.Materials and methodsThis experiment used the middle cerebral artery occlusion/reperfusion(MCAO/R)model in Sprague-Dawley(SD)rats as the experimental model.Fortyeight male SD rats were randomly divided into 4 groups and intraperitoneally injected with low-dose esketamine(LK,30 mg/kg)or high-dose esketamine(HK,60 mg/kg)10 minutes before ischemia,and the group Sham and group Model were injected with the same volume of saline.Neurobehavioral scores were performed 24 hours after cerebral ischemia/reperfusion,and then brain tissues of the ischemic cortex were collected.The Longa score and the modified neurological severity score(m NSS)were used to assess the degree of neurological deficits in rats.TTC staining was used to measure the volume of cerebral infarction.he extent of cerebral edema was assessed by the wet/dry weight method to measure brain tissue water content.To determine the level of oxidative stress in the ischemic brain tissue,the content of malondialdehyde(MDA)and activity of superoxide dismutase(SOD)were measured using commercial kits.The protein expression levels of Keap1,Nrf2 and HO-1 were detected using western blot analysis.Results1.The neurological behavior scores of the group LK and the group HK were significantly lower than those of the group Model(p < 0.05).There was no significant difference in the volume of cerebral infarction between the group LK and the group Model(p >0.05).However,the volume of cerebral infarction in the group HK was significantly reduced compared to the group Model(p <0.05).No significant difference observed in the degree of brain edema among the groups(p > 0.05).2.(1)Compared with the group Model,the SOD activity in the brain tissue of rats in the group HK increased significantly(p < 0.05).But there was no significant difference in SOD activity in the brain tissue of rats in the group LK(p > 0.05).The MDA levels in the brain tissue of rats in the group LK and the group HK decreased significantly with statistical significance(p < 0.05).(2)Compared with the group Model,the Nrf2 and HO-1 proteins in the group HK were significantly upregulated(p < 0.05).There was no significant change observed in the expression level of Keap1 among all groups(p > 0.05).ConclusionPre-treatment with intraperitoneal injection of esketamine can alleviate neurological dysfunction and reduce the infarct volume of ischemic brain tissue in rats following cerebral ischemia-reperfusion,and this effect is dose-dependent.However,it has no significant effect on the degree of cerebral edema.In addition,the SOD activity of the cortical tissue on the affected side was increased,while the MDA content was decreased,and the protein expression levels of Nrf2 and HO-1 were elevated.It is speculated that the Nrf2/HO-1 signaling pathway may be involved in the process of estketamine reducing oxidative stress damage. |
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