Hicks R R, Smith D H, Gennarelli T A, McIntosh T
Division of Physical Therapy, Annex I, University of Kentucky, Lexington 40536.
Brain Res. 1994 Aug 29;655(1-2):91-6. doi: 10.1016/0006-8993(94)91601-2.
Pharmacologic inhibition of excitatory amino acid neurotransmission improves physiologic, metabolic, and neurobehavioral outcome following experimental brain trauma. However, no studies to date have demonstrated pharmacologically-induced attenuation of histopathological changes associated with experimental brain injury models. The present study examined the effects of kynurenate, an NMDA and non-NMDA receptor antagonist, on neuronal survival in the hippocampus after lateral fluid-percussion brain injury in the rat. Animals (n = 10/treatment) randomly received an intravenous injection of either kynurenate (300 mg/kg) or buffer (equal volume) 15 min following fluid-percussion brain injury of moderate severity. Two weeks after injury, animals were sacrificed and neuronal cell loss in the hippocampus was examined with Nissl staining. Selective loss of neurons in the CA3 region of the hippocampus, which has previously been characterized in this model of brain injury, was found to be significantly attenuated following kynurenate treatment (P < 0.05). These data suggest that pharmacologic compounds which are known to have beneficial effects on neurobehavioral and physiological outcome following brain injury may also significantly attenuate post-traumatic neuronal cell loss. Our results also support other recent data that pharmacological intervention with an excitatory amino acid receptor antagonist may be of therapeutic value in the treatment of brain injury.
对兴奋性氨基酸神经传递进行药理抑制可改善实验性脑外伤后的生理、代谢及神经行为学结果。然而，迄今为止尚无研究表明药理学方法可减轻与实验性脑损伤模型相关的组织病理学变化。本研究检测了犬尿氨酸（一种NMDA和非NMDA受体拮抗剂）对大鼠侧脑液压冲击性脑损伤后海马神经元存活的影响。动物（每组10只）在中度严重程度的液压冲击性脑损伤后15分钟，随机接受静脉注射犬尿氨酸（300mg/kg）或缓冲液（等体积）。损伤后两周，处死动物，采用尼氏染色法检测海马区神经元细胞丢失情况。在该脑损伤模型中，海马CA3区神经元的选择性丢失此前已有描述，结果发现犬尿氨酸治疗后这种丢失明显减轻（P<0.05）。这些数据表明，已知对脑损伤后的神经行为和生理结果有有益作用的药理化合物，也可能显著减轻创伤后神经元细胞丢失。我们的结果还支持了其他近期数据，即使用兴奋性氨基酸受体拮抗剂进行药物干预可能对脑损伤治疗具有治疗价值。
