| Objective To observe the expression of TrkB and P75NTR protein in rat hippocampus 3 days after status epilepticus(SE) and the change of using of sheep BDNF neutralization antiserum(anti-BDNF).Investigate the role of TrkB and P75NTR in SE.Method 90 SD male rats are randomly divided into N.S.control group(10 rats),SE group(40 rats) and experiment group(40 rats).Rats of SE group are induced SE by LiCl-PILO i.p.Rats of experiment group received the same treatment as SE group,except for being injected with anti-BDNF 3h through lateral ventricle by stereo taxis before PILO i.p.Rats of both SE group and experiment group are randomly divided into 4 subgroups respectively(10 rats each),and are sacrificed 2h,6h,24,3d after SE ended.The changes of ethology of two groups during and after SE induced are observed and evaluated.Nissl stain is used to estimate the change of pathobiology of hippocampus.The expression of TrkB and P75NTR protein in hippocampus are detected with Western Blot.The expression and distribution of TrkB and P75NTR in hippocampal neuron membrane are detected with immunohistochemistry.Result1.Result of animal model:The achievement ratio of experiment group (respectively 90.7%and 73.77%),and mortality rate are lower than SE group (respectively 18.37%and 9.09%).Compared with SE group,the differences of mean dosage of PILO of experiment group(respectively 23.56±6.51mg/kg and 35.45±8.37mg/kg),mean time needed to induce SE(respectively 25.59±14.39min and 52.15±16.57min),mean persistent time of severe SE(respectively 47.42±3.88min and 25.29±6.84min)and mean dosage of 10%Chloral Hydrate for ending SE (respectively 0.35±0.58ml/100g and 0.29±0.08ml/100g) have significant statistic differences(p＜0.01).2.Rusult of Niss stain:There are progressive,selective numerous cell loss and necrotic in hippocampus duing acute phase after SE,especially CA1 area,lilus area emerges ectopic granule cells and abnormal pyramid neurons,while DG area present with marked proliferation within first week in SE group.The pathologic change of experiment group is similar with SE group,but the degree of cell loss and necrotic is much milder and recover faster(p＜0.05 or p＜0.01).3.Expression of TrkB is acute substantially down-regulated in SE group within 2h after SE ended,and arrives the lowest expression at 3d.There are significant statistic difference compared with control(p＜0.05 or p＜0.01)at 6h-3d after SE.Compared with control,the TrkB expression of experiment group is down-regulated at 2h,but up-regulated from 6h to 3d(p＜0.05 or p＜0.01).There are significant statistic difference compared with when TrkB expression of experiment group is ccompared with SE group at 6h-3d after SE(p＜0.05 or p＜0.01).4.Expression of P75NTR is acute substantially up-regulated in SE group within 2h after SE ended,and arrives peak at 3d.There are significant statistic difference compared with control(p＜0.05 or p＜0.01)in all four time points after SE.Compared with control,the P75NTR expression of experiment group is down-regulated at 2h, last to 3d(p＜0.05 or p＜0.01).There are significant statistic difference compared with when P75NTR expression of experiment group is ccompared with SE group in all detected time points(p＜0.05 or p＜0.01).Conclusion1.The changes of TrkB and P75NTR can promote neuronal death,inhibit the growth of axon and weaken synaptic function in SE.2.The treatment of anti-BDNF can decrease the action of endogenous BDNF protein,up-regulate TrkB and down-regulate P75NTR,delay the onset of SE and reduce the degree and duratuion of severe SE,has neural protective effect. |
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