Basic fibroblast growth factor and nerve growth factor administered in gel foam rescue medial septal neurons after fimbria fornix transection-猫眼课题宝

凝胶泡沫中施用碱性成纤维细胞生长因子和神经生长因子可挽救穹窿伞横断后的内侧间隔神经元

DOI：

发表时间：

1989

期刊：

Journal of Neuroscience Research

影响因子：

4.2

通讯作者：

中科院分区：

医学3区

文献类型：

作者：

D. Otto;M. Frotscher;K. Unsicker

碱性成纤维细胞生长因子(碱性成纤维细胞生长因子)是一种体外培养的胚胎神经元存活和递质促进剂。它的局部应用于受损的成人视神经和坐骨神经，已被证明可以挽救轴突切除的视网膜和感觉神经元，否则它们就会死亡。切断连接内侧隔(MS)和海马区的穹隆海马伞通路后，MS神经元经历严重的细胞死亡，这可以通过注射神经生长因子(NGF)来部分防止。在相同的损伤模式下，我们发现，在成年大鼠一侧穹隆海马伞切断后4周，甲酚紫染色显示87%的这些神经元已经消失。经8μg碱性成纤维细胞生长因子浸泡的明胶海绵植入后，神经元死亡率降至68%。0.3μg神经生长因子也有类似的抢救作用。20μg的神经生长因子可使细胞损失率降至54%。因此，碱性成纤维细胞生长因子和神经生长因子在20μg时挽救了22%和38%的本来会死亡的神经元。胆碱乙酰转移酶免疫细胞化学显示，与健侧相比，损伤侧胆碱能神经元显著减少。碱性成纤维细胞生长因子和神经生长因子可明显减少胆碱能神经元的死亡。与NGF相比，碱性成纤维细胞生长因子并不能阻止存活神经元胞体的缩小。考虑到成纤维细胞生长因子存在于脑和海马神经元中，我们的结果提示成纤维细胞生长因子可能在体内对中枢神经系统神经元起神经营养因子的作用。

Basic fibroblast growth factor (bFGF) recently has been established as a survival‐ and transmitter‐promoting neurotrophic agent for embryonic neurons in vitro. Its local application to lesioned adult optic and sciatic nerves has been shown to rescue axotomized retinal and sensory neurons that otherwise die. Following transection of the fimbria fornix pathway connecting the medial septum (MS) to the hippocampus, MS neurons undergo severe cell death, which can be prevented partially by infusion of nerve growth factor (NGF). In the same lesion paradigm, we find that 87% of these neurons visualized by cresyl‐violet staining have disappeared by 4 weeks after unilateral fimbria fornix transection in adult rats. Implantation of gel foam soaked with 8 μg bFGF reduced neuron death to 68%. A similar rescue effect was seen with 0.3 μg NGF. NGF administered at 20 μg reduced cell losses to 54%. Thus, bFGF rescued 22% and NGF at 20 μg 38% of the neurons that otherwise would have died. Choline acetyltransferase immunocytochemistry revealed dramatic losses of cholinergic neurons on the lesioned, compared with the unlesioned, side. Cholinergic neuron death was clearly reduced by the bFGF and NGF treatments. Basic FGF, in contrast to NGF, did not prevent a reduction in size of surviving neuronal cell bodies. Considered in the context of FGF being present in brain and hippocampal neurons, our results suggest a possible role for FGF as a neurotrophic factor for CNS neurons in vivo.