Indomethacin and dexamethasone treatment in experimental neoplastic spinal cord compression: Part 2. Effect on edema and prostaglandin synthesis.
Edema formation and prostanoid production (prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were studied in a model of neoplastic epidural cord compression (NSCC) in rats harboring a thoracolumbar tumor. Tumor-free and tumor-bearing animals were randomized for three treatments at 12-hour intervals with saline, dexamethasone (10 mg/kg i.p.), or indomethacin (10 mg/kg i.p.). Increase in water content was observed only in the compressed lumbar cord segments of paralyzed rats; the cervical and thoracic segments did not differ from controls. The rate of release of prostaglandins was evenly distributed along the spinal segments in tumor-free rats. In tumor-bearing rats, a consistent significant increase in PGE2 production was found in the compressed lumbar segment in the presence of neurological dysfunction: early (limp tail), P less than 0.05; paraplegia, P less than 0.001. A significantly elevated PGE2 synthesis preceded the increase in water content by 2 to 3 days. A 2-fold increase in TXB2 was detected in only one of three experiments, and synthesis of 6-keto-PGF1 alpha was elevated to 4 times the normal value (P less than 0.005) in two of three experiments. Dexamethasone failed to inhibit prostaglandin synthesis in the spinal cord of normal controls or paralyzed rats, whereas in nonneural tissues (liver, uterus) it reduced synthesis of the three metabolites by at least 50%, thus demonstrating a differential effect on central nervous system (CNS) vs. non-CNS tissues. Dexamethasone also failed to reduce the increased water content of the compressed segments.(ABSTRACT TRUNCATED AT 250 WORDS)
Siegal
T
T
Department of Neurology, Hadassah Hebrew University Hospital, Jerusalem, Israel.
Shohami
E
E
Shapira
Y
Y
Siegal
T
T
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001834:Body Water / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use*; D015232:Dinoprostone; D004487:Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007213:Indomethacin / Q000627:therapeutic use*; D011453:Prostaglandins / Q000096:biosynthesis; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000378:metabolism*; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D013120:Spinal Cord Neoplasms / Q000150:complications*; D013929:Thromboxane B2 / Q000096:biosynthesis
D011453:Prostaglandins; D011458:Prostaglandins E; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003907:Dexamethasone; D015232:Dinoprostone; D007213:Indomethacin