Spinal cord protection: effect of N-methyl-D-aspartate receptor antagonist MK-801 for spinal cord ischemia in a rabbit model.
Excitatory amino acids (glutamate, aspartate) play an important role in the ischemic cascade leading to cell death. The N-methyl-D-aspartate (NMDA) receptor is an excitatory amino acid (EAA) receptor, and NMDA receptor antagonists have been shown to exert a neuroprotective effect in central nervous system ischemia. The purpose of this study was to investigate the effects of noncompetitive NMDA receptor antagonists MK-801 and to observe the changes in EAAs after spinal cord ischemia in a rabbit model. Spinal cord ischemia was induced by clamping the infrarenal abdominal aorta for 24 min. Group 1 (n = 6) received no pharmacologic infusion. Group 2 (n = 5) was administered an intra-aortic hypothermic MK-801 (1 mg/kg) solution and group 3 (n = 6) was administered an intra-aortic normothermic MK-801 (2 mg/kg) solution immediately after clamping of the abdominal aorta. We evaluated the neurological function at 12, 24 and 48 hrs after spinal cord ischemia. A histopathologic study was carried out 72 hrs after spinal cord ischemia, and the results for groups 1 and 3 were compared. The glutamate and aspartate levels in the blood plasma were compared at pre-ischemia and at 12, 24, and 48 hrs among the groups. The perfusion of a normothermic MK-801 (2 mg/kg) solution significantly reduced the neurological dysfunction and the neuronal damage. There was a significant increase in aspartate at 24 and 48 hrs in group 1, but no such increase in glutamate occurred in groups 1 and 3. In conclusion, these data provide the evidence that therapeutic intervention with MK-801 (2 mg/kg) in the early period of spinal cord ischemia is beneficial in reducing neurological dysfunction and neuronal damage.
Tobinaga
S
S
Department of Surgery, Kurume University School of Medicine, Japan.
D000818:Animals; D001224:Aspartic Acid / Q000097:blood; D016291:Dizocilpine Maleate / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000097:blood; D007511:Ischemia / Q000188:drug therapy*; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D018698:Glutamic Acid; D016291:Dizocilpine Maleate