Protective effect of the NMDA antagonist MK-801 on photochemically induced spinal lesions in the rat.
Photochemically induced ischemic lesions in the rat spinal cord were studied using neurological tests and morphological evaluation in order to investigate ischemia-mediated pathophysiological mechanisms in traumatic spinal cord injury. One week after ischemic lesioning, animals were severely impaired with 85% decrease of performance in neurological tests. During the next 2 weeks considerable recovery occurred. Pretreatment with the noncompetitive N-methyl-D-aspartate antagonist MK-801 at a dose of 0.5-1.0 mg/kg significantly improved the recovery of function after spinal ischemia while lower doses exerted no protection. Morphologically, no dose-response effect on the extent of tissue necrosis was found, but a significant difference between groups with severe neurological deficit versus mildly affected groups was observed. Immunohistochemical staining for glial fibrillary acidic protein in the area close to the lesion revealed extensive gliosis, while neurofilament immunohistochemistry showed an irregular pattern of fiber loss with large variability between animals. The degree of gliosis or loss of neurofilament immunoreactivity in nonnecrotic tissue was not affected by MK-801. These results suggest that excessive stimulation of N-methyl-D-aspartate receptors participates in the development of spinal cord ischemia and possibly also participates after traumatic spinal cord injury.
Hao
J X
JX
Department of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
Watson
B D
BD
Xu
X J
XJ
Wiesenfeld-Hallin
Z
Z
Seiger
A
A
Sundström
E
E
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000528:radiation effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007511:Ischemia / Q000139:chemically induced / Q000473:pathology*; D007834:Lasers; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009410:Nerve Degeneration; D016900:Neurofilament Proteins / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000098:blood supply* / Q000473:pathology
D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate