Experimental neoplastic spinal cord compression: effect of anti-inflammatory agents and glutamate receptor antagonists on vascular permeability.
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)
Siegal
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Department of Neurology, Hadassah Hebrew University Hospital, Jerusalem, Israel.
Siegal
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Lossos
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D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics*; D002199:Capillary Permeability / Q000187:drug effects*; D003907:Dexamethasone / Q000493:pharmacokinetics; D003986:Dibenzocycloheptenes / Q000493:pharmacokinetics / Q000494:pharmacology; D016291:Dizocilpine Maleate; D007213:Indomethacin / Q000493:pharmacokinetics; D007649:Ketamine / Q000493:pharmacokinetics / Q000494:pharmacology; D008775:Methylprednisolone / Q000493:pharmacokinetics; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013116:Spinal Cord / Q000378:metabolism*; D013117:Spinal Cord Compression / Q000378:metabolism*; D013120:Spinal Cord Neoplasms / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D003986:Dibenzocycloheptenes; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D007649:Ketamine; D016291:Dizocilpine Maleate; D003907:Dexamethasone; D008775:Methylprednisolone; D007213:Indomethacin