Experimental neoplastic spinal cord compression: effect of ketamine and MK-801 on edema and prostaglandins.
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.
Siegal
T
T
Department of Neurology, Hadassah Hebrew University Hospital, Jerusalem, Israel.
Siegal
T
T
Shohami
E
E
Lossos
F
F
D000704:Analysis of Variance; D000818:Animals; D001929:Brain Edema / Q000188:drug therapy*; D003986:Dibenzocycloheptenes / Q000494:pharmacology* / Q000627:therapeutic use; D016291:Dizocilpine Maleate; D004487:Edema / Q000378:metabolism / Q000503:physiopathology*; D018219:Histiocytoma, Benign Fibrous / Q000378:metabolism / Q000503:physiopathology*; D007649:Ketamine / Q000494:pharmacology* / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology; D013117:Spinal Cord Compression / Q000503:physiopathology*; D013120:Spinal Cord Neoplasms / Q000378:metabolism / Q000503:physiopathology*
D003986:Dibenzocycloheptenes; D011453:Prostaglandins; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D007649:Ketamine; D016291:Dizocilpine Maleate