Ng W P, Cartel N, Roder J, Roach A, Lozano A
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Brain Res. 1996 May 13;720(1-2):17-24. doi: 10.1016/0006-8993(96)00062-5.
In vitro and animal studies have identified molecules in mammalian CNS myelin which inhibit neuritic extension and which may be responsible, at least in part, for the lack of axonal regeneration after injury in the injured brain, optic nerve and spinal cord. To determine whether such inhibitory activity may be present in human CNS myelin, we used a bioassay to characterize neurite outgrowth on this substrate. Human CNS myelin strongly inhibited neuritic outgrowth from newborn rat dorsal root ganglion neurons and NG-108-15 cells, a neuroblastoma-glioma hybrid cell line. Similar but less potent inhibitory activity was identified in human gray matter. The CNS myelin inhibition of neuritic outgrowth appeared to be dependent on direct contact between the myelin substrate and neurites. The inhibitory activity in human CNS myelin closely resembled that described in adult rodents. Inhibition of neurite growth by human CNS myelin in this in vitro bioassay mirrors the lack of regeneration in vivo and can be used as a model to develop strategies designed to enhance axonal regeneration and neural recovery.
体外和动物研究已在哺乳动物中枢神经系统髓磷脂中鉴定出一些分子,这些分子会抑制神经突延伸,并且至少在一定程度上可能是造成受伤大脑、视神经和脊髓损伤后轴突再生缺失的原因。为了确定人类中枢神经系统髓磷脂中是否存在这种抑制活性,我们使用了一种生物测定法来表征在这种底物上的神经突生长情况。人类中枢神经系统髓磷脂强烈抑制新生大鼠背根神经节神经元和NG-108-15细胞(一种神经母细胞瘤-胶质瘤杂交细胞系)的神经突生长。在人类灰质中也发现了类似但效力较弱的抑制活性。中枢神经系统髓磷脂对神经突生长的抑制作用似乎取决于髓磷脂底物与神经突之间的直接接触。人类中枢神经系统髓磷脂中的抑制活性与成年啮齿动物中描述的抑制活性非常相似。在这种体外生物测定法中,人类中枢神经系统髓磷脂对神经突生长的抑制反映了体内再生的缺乏,并且可以用作开发旨在增强轴突再生和神经恢复策略的模型。