In an experimental rat model of neoplastic spinal cord compression, the in vivo effect of steroidal and non-steroidal anti-inflammatory agents on the water content, prostaglandin E2 (PGE2) production, and specific gravity of the compressed cord segments were assessed, as well as the effect on the course of the disease. Paraplegic animals presented a consistent increase in the water content, PGE2 synthesis, and specific gravity in the compressed cord segments. The effect of treatment given on onset of paraplegia with either dexamethasone sodium phosphate (Dex-p; 10 mg/kg twice dally), or free dexamethasone (F-dex; 8.25 mg/kg twice dally) or indomethacin (10 mg/kg twice daily), was evaluated after 30 hours of therapy. Both F-dex and indomethacin eliminated spinal cord edema but varied in the rate of inhibitory effect on PGE2 production (dexamethasone less than indomethacin). Dexamethasone sodium phosphate failed to reduce spinal cord edema and PGE2 synthesis, but specific gravity changes were corrected by each of the administered agents. Evaluation of the effect of treatment on the course of the disease required dose reduction by 50% for Dex-p and F-dex, and to 25% for Indomethacin, to avoid lethal toxicity. Treatment was started on appearance of the first sign of neurologic dysfunction (Grade 1) and continued to paraplegia (Grade 5). In the saline-treated rats, the mean time Interval between Grades 1 and 5 was 2.7 ± 0.3 days. Free dexamethasone, Dex-p, and Indomethacin significantly prolonged this interval by 57%, 54%, and 48% respectively (P < 0.005). The three agents differed in their ability to control the increases in water content and in PGE2 production, but proved almost equally effective in the prompt control of the specific gravity changes. Thus it appears that the effective control of specific gravity deviations, rather than the antiedematous effect, contributes most to the delay in the onset of paraplegia.
*department of Neurology, Hadassah Hebrew University Hospital, Jerusalem, Tel-Aviv, Israel.
‡department of Oncology, Hadassah Hebrew University Hospital, Jerusalem, Tel-Aviv, Israel.
§department of Pharmacology, and Anaesthesiology, Hadassah Hebrew University Hospital, Jerusalem, Tel-Aviv, Israel.
†department of Assuta Hospital, Tel-Aviv, Israel.