Nakamichi T
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Jpn J Thorac Cardiovasc Surg. 1998 Sep;46(9):854-9. doi: 10.1007/BF03217833.
Evidence is accumulating that glutamate, a major neurotransmitter, exerts potent neurotoxic activity during ischemia. In our laboratory, a delayed-onset paraplegia model using rabbits has been developed and described. The severity of the ischemic event in this model, i.e., extracellular glutamate overload, is believed to influence the etiology of this borderline lesion. We hypothesized that glutamate receptor antagonists (MK-801, NBQX) would attenuate the delayed neuronal dysfunction that follows spinal cord ischemia. Infrarenal aortic segments from 18 New Zealand white rabbits were isolated for 5 minutes and infused at a rate of 2 ml/min. Group I (n = 6) received normothermic L-glutamate (20 mM). Group II (n = 6) received 3 mg of MK-801 and normothermic L-glutamate (20 mM). Group III (n = 6) received 3 mg of NBQX and normothermic L-glutamate (20 mM). Neurologic function was assessed at 6, 24, and 48 hours after surgery according to the modified Tarlov scale. After 48 hours, the rabbits were euthanized and spinal cords were harvested for histologic examination. The neurologic function of three rabbits in group I showed acure paraplegia and the other three showed delayed-onset paraplegia, whereas all group II animals had nearly intact neurologic function and all group III animals showed mild neurologic disturbance. Histologic examination of spinal cords from rabbits in group I showed evidence of moderate spinal cord injury with necrosis of central gray matter and adjacent white matter and axonal swelling, whereas spinal cords from group II showed small and localized spinal cord injuries and those from group III revealed no evidence of cord injury. These results indicate that MK-801 and NBQX exert different neuroprotective effects related to different mechanisms of glutamate neurotoxicity mediated by the NMDA receptor and non-NMDA receptor, which initiate a deleterious cascade of biochemical events that ultimately results in delayed-onset paraplegia.
越来越多的证据表明，谷氨酸作为一种主要的神经递质，在缺血期间会发挥强大的神经毒性作用。在我们实验室，已建立并描述了一种使用兔子的迟发性截瘫模型。该模型中缺血事件的严重程度，即细胞外谷氨酸过载，被认为会影响这种临界病变的病因。我们假设谷氨酸受体拮抗剂（MK - 801、NBQX）会减轻脊髓缺血后延迟出现的神经元功能障碍。从18只新西兰白兔分离出肾下腹主动脉段5分钟，并以2毫升/分钟的速度进行灌注。第一组（n = 6）接受常温L - 谷氨酸（20毫摩尔）。第二组（n = 6）接受3毫克MK - 801和常温L - 谷氨酸（20毫摩尔）。第三组（n = 6）接受3毫克NBQX和常温L - 谷氨酸（20毫摩尔）。术后6小时、24小时和48小时根据改良的塔尔洛夫量表评估神经功能。48小时后，对兔子实施安乐死并取出脊髓进行组织学检查。第一组中三只兔子的神经功能表现为急性截瘫而另外三只表现为迟发性截瘫，而第二组所有动物的神经功能几乎完好，第三组所有动物表现出轻度神经功能障碍。对第一组兔子脊髓的组织学检查显示有中度脊髓损伤的证据，包括中央灰质和相邻白质坏死以及轴突肿胀，而第二组兔子的脊髓显示有小的局限性脊髓损伤，第三组兔子的脊髓未显示脊髓损伤迹象。这些结果表明，MK - 801和NBQX通过NMDA受体和非NMDA受体介导的谷氨酸神经毒性的不同机制发挥不同的神经保护作用，这些机制引发了一系列有害的生化事件，最终导致迟发性截瘫。
