Dexamethasone and indomethacin do not affect brain edema following head injury in rats.
Head trauma was induced in rats by a weight-drop device, falling over the exposed skull over the left hemisphere. The neurological state of the rats was evaluated by a neurological severity score at 1 h and 18 h post head trauma. At 18 h post head trauma, rats were decapitated and tissue from the vicinity of the injury and from a corresponding area in the contralateral hemisphere was taken for specific gravity (SG) determination using linear gradient columns. Slices were taken from the same sites for incubation in Krebs-Ringer solution, and the concentrations of prostaglandin (PG)E2, 6-keto-PGF1 alpha, and thromboxane B2 accumulated in the medium during 1 h were measured by radioimmunoassay. In one experimental group, rats were pretreated with intraperitoneal dexamethasone sodium phosphate (4 mg/kg) 18 and 2 h before head trauma, and a third dose was given 8 h post head trauma. Another group was treated with intraperitoneal indomethacin (10 mg/kg) 1 h before and 7 h after head trauma. Other groups were treated immediately and 8 h after head trauma with 4, 8, 15, or 30 mg/kg of dexamethasone sodium phosphate. Another group of rats was treated with free dexamethasone (10 mg/kg) right after head trauma and 8 h later. Head trauma induced edema, as expressed by decreased SG, in the left hemisphere of all traumatized rats. Neither treatment protocol affected the neurological severity score of the injured rats or the SG of the contused hemisphere. PG synthesis, on the other hand, was significantly reduced following indomethacin or free dexamethasone, both in sham and traumatized rats, but not in dexamethasone sodium phosphate-treated rats. We conclude that pretreatment with indomethacin, dexamethasone sodium phosphate, or dexamethasone, used in the present protocols, does not affect posttraumatic cerebral edema. Thus, the role of PGs as mediators of edema formation remains unclear.
Shapira
Y
Y
Department of Anesthesiology, Hebrew University Hadassah Medical School, Jerusalem, Israel.
Davidson
E
E
Weidenfeld
Y
Y
Cotev
S
S
Shohami
E
E
D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000209:etiology* / Q000473:pathology; D006259:Craniocerebral Trauma / Q000150:complications* / Q000503:physiopathology; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009420:Nervous System / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012720:Severity of Illness Index; D013046:Specific Gravity
C004180:dexamethasone 21-phosphate; D003907:Dexamethasone; D007213:Indomethacin