A potential role for excitotoxins in the pathophysiology of spinal cord injury.
It has been proposed that endogenously released excitatory amino acids may contribute to injury of the central nervous system in a variety of disorders including certain neurodegenerative diseases, epilepsy, and cerebral ischemia. In the present studies we evaluated the hypothesis that excitatory amino acids, acting at the N-methyl-D-aspartate (NMDA) receptor, contribute to secondary tissue damage following traumatic spinal cord injury. Administration of NMDA, adjacent to the trauma site, significantly worsened the outcome after thoracic cord injury in rats, whereas its stereoisomer, N-methyl-L-aspartate (NMLA), was without effect. Systemic treatment with MK-801--a selective, centrally active, NMDA antagonist--significantly improved neurological outcome after trauma. These findings extend the excitotoxin concept to central nervous system trauma and indicate that NMDA antagonists may be beneficial in the treatment of traumatic spinal cord injury.
Faden
A I
AI
Department of Neurology, University of California, San Francisco.
Simon
R P
RP
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013237:Stereoisomerism; D014118:Toxins, Biological / Q000502:physiology*
D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D014118:Toxins, Biological; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate