dizocilpine-maleate and Spinal-Cord-Neoplasms

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.

Topics: Analysis of Variance; Animals; Brain Edema; Dibenzocycloheptenes; Dizocilpine Maleate; Edema; Histiocytoma, Benign Fibrous; Ketamine; Neurons; Prostaglandins; Rats; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter; Spinal Cord Compression; Spinal Cord Neoplasms

It has been demonstrated in paraplegic rats harboring an epidural neoplasm that an antiedema effect can be achieved by in vivo treatment with either steroidal or nonsteroidal anti-inflammatory agents or by glutamate receptor antagonists. The effect of these treatments on vascular permeability of the normal and compressed spinal cord was quantitated by the Evans blue dye technique. Tumor-free and tumor-bearing rats were assigned randomly for treatment as follows: 0.5 ml of saline or three doses at 12-hour intervals of either dexamethasone (5 mg/kg), methylprednisolone (30 mg/kg), indomethacin (5 mg/kg every 24 hours), or a single dose of either ketamine (110 mg/kg) or MK-801 (3 mg/kg). Treatment was given at the onset of paraplegia, and the animals were killed after 30 hours. In tumor-bearing rats in the early symptomatic stage, extravasation of Evans blue dye was 4.8 times greater than that of the normal cord (P less than 0.001) and at the onset of paraplegia it was 9.9 times greater (P less than 0.0006). Glucocorticoids and indomethacin reduced dye extravasation in paraplegic animals (P less than 0.01 and P less than 0.003, respectively), but the decreased permeability induced by ketamine and MK-801 did not reach the level of significance. In tumor-free control animals permeability was not changed by administration of either glucocorticoids or indomethacin but was significantly reduced by ketamine or MK-801 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anti-Inflammatory Agents; Capillary Permeability; Dexamethasone; Dibenzocycloheptenes; Dizocilpine Maleate; Indomethacin; Ketamine; Methylprednisolone; Rats; Receptors, Glutamate; Receptors, Neurotransmitter; Spinal Cord; Spinal Cord Compression; Spinal Cord Neoplasms