Excitotoxin-induced neural tissue damage is mediated through specific receptors. We studied the in vivo effect of two selective
N-methyl-D-aspartate receptor antagonists on the compressed spinal cord segments of rats harboring a thoracolumbar
epidural tumor. The effect of a single intramuscular treatment with either
MK-801 (3 mg/kg) or
ketamine (110 mg/kg) given at the onset of
paraplegia was evaluated 30 hours later. In saline-treated control animals, significant increases in water content,
prostaglandin E2, and 6-keto-prostaglandin F1 alpha were evident. Treatment with either agent resulted in a normal water content in the compressed segments but had no effect on
prostaglandin synthesis. Evaluation of the effect of treatment on the course of the disease required
dose reduction by 45% for
ketamine and by 30% for
MK-801, to avoid the excessive
sedative effect. Treatment was started at the first appearance of neurological dysfunction (Grade 1) and continued to
paraplegia (Grade 5). The mean time interval between Grades 1 and 5 was 2.1 +/- 0.3 days in saline-treated control animals, and it was not significantly altered by either
ketamine or
MK-801. Our study indicates that in the end stage of epidural compression, when
ischemia is present,
excitotoxins probably participate in the evolution of a cytotoxic
edema. It is suggested that treatment initiated at the onset of
paraplegia may still reduce the cytotoxic
edema, but its potential clinical value requires further investigations.