The Effects Of Nogo-A And Nogo Recepter Antagonists In Newborn Rats With Hypoxic Ischemic Brain Damage

Objective The hypoxic-ischemic encephalopathy(HIE)caused by asphyxia in peripartum is a serious disease in newborn infants,with a high disability rate and mortality rate.The most important question is that the center nerve system was not able to regenerate after injury.The traditional symptomatic treatment can not improve the prognosis effectively.But lots of studies in recent years discovered that there were factors caused the failure of regeneration.At present,there were at least three factors were found in center neural myelin sheath to produce marked effects:Nogo-A,myelin-associated glycoprotein(MAG), oligodendrocyte-myelin glycoprotein(OMgp).Nogo-A was able to produce a most important effect.There was a structural domain composed by 66 amino acids in carboxyl terminus.All the three inhibiting factors effected by combined with nogo receptor.NEP1-40 was designed to aim directly at the structural domain,and it can antagonize the combination competitively. Ganglioside was commonly used to treat HIBD,it can stabilize the cellular membrane,ease cellular edema,prevent the accumulation of Ca²⁺, antagonize the neurotoxicity of excitatory amino acids.In this study, HIBD model of newborn rats were prepared,then NEP1-40 and GM-1 were injected in their belly cavity respectively.After got the brain tissue, the weights of brains,the pathological change,the contents of Nogo-A mRNA were observed to investigate the function of Nogo-A,the effects of NEP1-40 and GM-1 in the newborn rats with hypoxic ischemic brain damage (HIBD). Methods 100 rats were randomly divided into 10 groups:normal control group,sham operated group,HIBD model group,NEP1-40 treatment group and GM-1 treatment group after HIBD at 6h and 24h.HIBD model groups were prepared by Rice method,NEP1-40(10mg/kg)and GM-1(20mg/kg)were injected in the belly cavity of two treatment groups respectively,while,normal sodium(0.25ml/kg)were injected in the belly cavity of the normal control groups,sham operated groups,and HIBD model groups.The tissues were fixed in 30%sugar solution with 4%polyoxymethylene.Then the tissues were prepared by the frozen microtome section.The pathological changes were observed by HE drum dyeing,and the contents of Nogo-A mRNA were detected by the method of in situ hybridization.Resultsâ‘ The expression of Nogo-A mRNA in HIBD groups was higher than that in control groups at both time points.In the HE section,The nerve cells were edematous,Nissl's bodies were necrotic,and the endothelial cells of the choroid plexus were not complete.â‘¡In NEP1-40 groups,the expression of Nogo-A mRNA were lower than that in HIBD groups at both time points.The nerve cells were edematus lightly,and the endothelial cells and capillaries of the choroid plexus were mostly normal.â‘¢There was no great difference between the GM-1 group and HIBD group when they were treated at the 6th hour.And for the 24th-hour-group,the expression in GM-1 group was lower than that of HIBD group but higher than that of normal control group.The cellular edema was eased than in HIBD model groups, and the choroid plexus were incomplete partly.Conclusion Nogo-A mRNA increased obviously in the newborn rats with HIBD. Nogo-A encoded by the mRNA can inhibit the regeneration of central nerve after being injured,and NEP1-40 can antagonize the function,and be able to ease cellular edema,to improve the regional flow supply of the injured nerve,thereby it can promote the regeneration.GM-1 was also able to antagonize the expression of mRNA,to stabilize the cellular membrane, to ease cellular edema of the injured nerve and to accelerate the regeneration of new nerve.