Pretreatment with NMDA receptor antagonist MK801 improves neurophysiological outcome after an acute spinal cord injury.
The post-traumatic release of excitatory amino acids (EAA) and their actions on N-methyl-D-aspartate (NMDA) receptors plays a major role in the spinal cord secondary injury process. The neuronal damage caused by the release of EAA may be reduced by NMDA-receptor channel blockers. To investigate the involvement of NMDA receptors in spinal cord injury (SCI), we pretreated animals with the noncompetitive NMDA antagonist MK801 (1.0 mg kg-1) before a compressive acute SCI. Pretreated animals with MK801 significantly (p = 0.038) improved the recovery of function as measured by evoked potential activities. Morphologically, specimens from rats treated with MK801 were characterized by milder and more localized hemorrhage in the gray matter. Immunohistochemical staining for glial fibrillary acidic protein (GFAP) and neurofilament (NF) histochemistry showed leakage of these antigens in traumatized cord while characteristic staining of astrocytes and neurons and their processes was observed in morphologically preserved tissue. The loss of NF immunoreactivity was reduced by MK801 treatment.
Haghighi
S S
SS
Section Neurosurgery, University of Nebraska Medical Center, Omaha 68105, USA.
Johnson
G C
GC
de Vergel
C F
CF
Vergel Rivas
B J
BJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D007150:Immunohistochemistry; D009408:Nerve Compression Syndromes / Q000188:drug therapy / Q000503:physiopathology; D009431:Neural Conduction / Q000187:drug effects; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000737:chemistry; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate