von Euler M, Seiger A, Holmberg L, Sundström E
Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Hydding University Hospital, Sweden.
Exp Neurol. 1994 Sep;129(1):163-8. doi: 10.1006/exnr.1994.1157.
We have used the laser-induced photochemical thrombosis model in adult rats to evaluate the significance of the non-N-methyl-D-aspartate (non-NMDA) subtype of glutamate receptors in situations of focal spinal cord ischemia. The animals were pretreated with the selective non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)-quinoxaline (NBQX) or, for comparison, the NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5-10-imine (MK-801). Neurological function was quantified using evaluations of motor score and inclined plane. The MK-801-treated rats had higher motor scores during the 3-week observation period while NBQX-treated rats only performed significantly better at 1 week. Both treatments caused significantly better performance in the inclined plane test. NBQX and MK-801 reduced the volume of necrosis by approximately 47% at 3 weeks postlesion. We conclude that blockade of both NMDA and non-NMDA subtypes of glutamate receptors reduces ischemic necrosis, possibly by preventing excessive stimulation of these receptors by released excitatory amino acids in the lesion area.
我们利用成年大鼠的激光诱导光化学血栓形成模型，来评估谷氨酸受体的非N-甲基-D-天冬氨酸（非NMDA）亚型在局灶性脊髓缺血情况下的重要性。动物预先接受选择性非NMDA拮抗剂2,3-二羟基-6-硝基-7-氨磺酰基苯并[f]喹喔啉（NBQX）处理，或者作为对照，接受NMDA拮抗剂（+）-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺（MK-801）处理。通过运动评分和倾斜平面评估来量化神经功能。在3周的观察期内，接受MK-801处理的大鼠运动评分更高，而接受NBQX处理的大鼠仅在1周时表现明显更好。两种处理在倾斜平面试验中均使表现显著改善。在损伤后3周，NBQX和MK-801使坏死体积减少了约47%。我们得出结论，阻断谷氨酸受体的NMDA和非NMDA亚型均可减少缺血性坏死，这可能是通过防止损伤区域释放的兴奋性氨基酸对这些受体的过度刺激来实现的。
