NBQX, a competitive non-NMDA receptor antagonist, reduces degeneration due to focal spinal cord ischemia.
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.
von Euler
M
M
Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Hydding University Hospital, Sweden.
Seiger
A
A
Holmberg
L
L
Sundström
E
E
D000704:Analysis of Variance; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology; D007834:Lasers; D009410:Nerve Degeneration / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D012016:Reference Values; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016291:Dizocilpine Maleate