Neuroprotection Of Gm1 For Neuronal Injury Of Developmental Brain Induced By Ketamine In Rat

Background: Ketamine is a commonly used general anesthetic in pediatric patients.Most preclinical studies have shown that animals exposed to ketamine during the critical period of brain development may lead to widespread neurodegeneration and long-term cognitive impairment later in life.Some scholars have found that ketamine impairs the recognition memory,possibly by preventing the expression levels of brain-derived neurotrophic factor(BDNF)in the hippocampus.Since exogenous monosialotetrahexosylganglioside(GM1)can not only promote the recovery of central lesion,but also induce the synthesis and release of brain-derived neurotrophic factor,therefore,we speculate that GM1 can alleviate the neurotoxicity of ketamine on the developmental brain by increasing the release of brain-derived neurotrophic factor.Objective: To explore the effect and mechanism of exogenous GM1 on developmental brain injury induced by ketamine.Methods: Experiments were conducted on SPF Sprague-Dawley postnatal day 5(P5)rat pups.Rats were randomly divided into control group,ketamine group,GM1 group,ketamine+GM1 group,ketamine+GM1+Ig Y group,ketamine+GM1+anti-BDNF group.P7 rat pups were anesthetized using ketamine to develop the model of anesthesia.Rat pups in control group received intraperitoneal injections of equal volume of saline to GM1 every day from P5-P7,in addition,P7 rats received five intraperitoneal injections of equal volume of saline to ketamine.Rat pups in ketamine group received intraperitoneal injections of equal volume of saline to GM1 every day from P5-P7,P7 rats received five intraperitoneal injections(20 mg/kg each)of ketamine at 90 min intervals over 6 h.Rat pups in GM1 group received intraperitoneal injections of GM1(30 mg/kg each)at a time every day from P5-P7,P7 rats received five intraperitoneal injections of equal volume of saline to ketamine.Rats in ketamine+GM1 group were intraperitoneal injected of GM1 as follows,P7 rats were intraperitoneal injected of ketamine as follows,insure that P7 rats received GM1 1 h after the last injection of ketamine.After GM1 were intraperitoneal injected,Ig Y and anti-BDNF(100 ug/kg each)were respectively delivered by intranasal administration to rats of ketamine+GM1+Ig Y group and ketamine+GM1+anti-BDNF group every day from P5-P7.One third of every group’s rats were tested in the Morris water maze every day from P32-P37,to detect the behavior changes.TUNEL cell apoptosis assay kit was used to detect the number of neuronal apoptosis in hippocampal dentate gyrus(DG)area.Western blot was used to detect the protein expression level of cleaved-caspase 3,BDNF,p-AKT and p-ERK in hippocampus.Results: 1.Ketamine induced cognitive impairment in P7 rats and widespread neural apoptosis in hippocampal DG area,at the mean while,exogenous GM1 alleviated cognitive impairment and reduced neural apoptosis induced by ketamine.2.GM1 promoted the protein expression level of BDNF,p-AKT and p-ERK in hippocampus of neonatal rats.3.Anti-BDNF suppressed the protection of GM1 on cognitive impairment and neural apoptosis induced by ketamine.4.Anti-BDNF suppressed the protein expression level of BDNF,p-AKT and p-ERK in hippocampus of neonatal rats.Conclusion: GM1 can alleviate the neurotoxicity of ketamine on the developmental brain by increasing the expression level of BDNF.