Vandenberghe W, Van Den Bosch L, Robberecht W
Department of Neurology, University Hospital Gasthuisberg, Leuven, Belgium.
Neuroreport. 1998 Aug 24;9(12):2791-6. doi: 10.1097/00001756-199808240-00020.
Spinal motoneurons are highly vulnerable to kainate both in vivo and in vitro. Tissue-type plasminogen activator (tPA) and plasmin have recently been shown to mediate kainate-induced neuronal death in the mouse hippocampus in vivo. The aim of the present study was to determine whether tPA also mediates the kainate-induced death of motoneurons in vitro. A motoneuron-enriched neuronal population was isolated from the ventral spinal cord of wild-type (WT) and tPA-deficient (tPA-/-) mouse embryos. WT and tPA-/- neurons were cultured on WT and tPA-/- spinal glial feeder layers, respectively. WT and tPA-/- co-cultures were morphologically indistinguishable. Expression of tPA in WT co-cultures was demonstrated using RT-PCR. WT and tPA-/- co-cultures were exposed to kainate for 24 h. The neurotoxic effect of kainate did not differ significantly between WT and tPA-/- cultures. The plasmin inhibitor alpha2-antiplasmin did not protect WT neurons against kainate-induced injury. These results indicate that the plasmin system is not a universal mediator of kainate-induced excitotoxicity.
在体内和体外，脊髓运动神经元对红藻氨酸都高度敏感。组织型纤溶酶原激活物（tPA）和纤溶酶最近已被证明在体内介导小鼠海马体中红藻氨酸诱导的神经元死亡。本研究的目的是确定tPA是否也在体外介导红藻氨酸诱导的运动神经元死亡。从野生型（WT）和tPA基因缺陷型（tPA-/-）小鼠胚胎的腹侧脊髓中分离出富含运动神经元的神经元群体。WT和tPA-/-神经元分别在WT和tPA-/-脊髓胶质饲养层上培养。WT和tPA-/-共培养物在形态上没有区别。使用逆转录-聚合酶链反应（RT-PCR）证明了WT共培养物中tPA的表达。WT和tPA-/-共培养物暴露于红藻氨酸24小时。红藻氨酸的神经毒性作用在WT和tPA-/-培养物之间没有显著差异。纤溶酶抑制剂α2-抗纤溶酶不能保护WT神经元免受红藻氨酸诱导的损伤。这些结果表明，纤溶酶系统不是红藻氨酸诱导的兴奋性毒性的普遍介质。
