神经生长因子及其高亲和力受体在脊髓损伤大鼠大脑运动皮质及皮质脊髓束的表达

EXPRESSION OF NGF AND TrkA IN THE MOTOCORTEX AND CORTICOSPINAL TRACT OF THE RAT FOLLOWING SPINAL CORD INJURY

目的 探讨脊髓损伤后大脑运动皮质及皮质脊髓束内神经生长因子 (NGF)及其高亲和力受体 (TrkA)表达的变化。 方法 成年SD大鼠 ,随机分为正常对照组、假手术组、脊髓损伤 (SCI)组。参照Allen重击法 ,重击SCI组动物T1 2 节段脊髓背侧 ,顿挫损伤双侧皮质脊髓侧束 ,按损伤后存活时间将动物分为SCI 1d组、SCI 2d组、SCI5d组。各组大脑及脊髓切片经ABC法免疫组织化学染色 ,光镜及电镜观察 ,并用图像分析技术对结果进行分析。结果 脊髓损伤后上述部位酪氨酸蛋白激酶A(TrkA)的表达随SCI后动物存活时间的延长明显上调 ,电镜观察发现损伤后的皮质脊髓侧束轴浆内有TrkA免疫反应阳性产物积聚 ,轴膜上亦有免疫反应产物分布 ,且轴索末端有生芽现象 ;皮质脊髓侧束的神经纤维内可见串珠状的NGF免疫反应阳性产物 ,束内NGF阳性胶质细胞亦随动物术后存活时间的延长逐渐增多。 结论 脊髓损伤可刺激大脑相应区域运动皮质锥体细胞表达TrkA并向其轴突末梢运输定位于轴膜 ,以摄取损伤局部胶质细胞等产生的NGF ,后者借逆向轴浆运输运回胞体 ,维持锥体细胞的存活及促进其轴突的再生。

Objective To explore the changes of NGF and TrkA expression in the motocortex and corticospinal tract of rat following spinal cord injury. Methods Adult SpragueDawlay rats were divided into three groups at random:1. Normal control group(n=5); 2. Sham operation group(n=5); 3. SCI(spinal cord injury) group(n=15), according to the postoperative survival time, animals of this group were randomly subdivided into SCI 1d group, SCI 2d group and SCI 5d group. The animals of these subgroups suffered from Allen’s weightdrop SCI operation on T-{12} spinal cord. The expression of TrkA and NGF in the motocortex and the lateral corticospinal tract of spinal cord was examined by immunohistochemistry using light and electron microscopy. Results After the SCI operation, the expression of TrkA in pyramidal cells of the motocotex was upregulated gradually and the expression of NGF in gliocytes of the corticospinal tract was upregulated as well. In addition to abovementioned results, sprouts of axons in the injured corticospinal tract were observed by light and electron microscopy, in the sprouts there was NGF or TrkA immunoreactive product. NGF and TrkA immunoreactive products were accumulated in the axoplasm of the corticospinal tract, more densely in the terminal of injured axons especially.Conclusion The results suggest that there are intrinsic regeneration mechanisms in the injured spinal cord. Signals of SCI may irritant pyramidal cells of the motocotex to synthesize TrkA then transport it to the end of axons and deposit it on the axolemma. Contemporaneously, the gliocytes of the corticospinal tract can synthesize and secrete NGF; NGF can bind to TrkA and then form the NGFTrkA complex which is communicated retrogradely to the pyramidal cell body and play an important role in the neuroregeneration.;