title: OKY-046 inhibits thromboxane synthesis with no effect on brain edema and neurological status in head traumatized rats.
abstract: Head trauma (HT) was induced in the left hemisphere of rats by a weight drop device. Edema was maximal 24 h after HT in the injured zone, and PGE2, TXB2 and 6-keto-PGF1 alpha were elevated in both the injured and remote areas. The effect of a specific thromboxane synthetase inhibitor, OKY-046, on the outcome of HT was studied. OKY-046, 100 mg/kg, was given to rats immediately and 8 h after HT. The neurological severity score (NSS) was evaluated at 1 h after HT, and at 24 h, just prior to sacrifice. Specific gravity (SG) of both hemispheres was measured after decapitation. Prostaglandins (PGs) were extracted from the site of injury and from the frontal lobes, remote from the injury, and assayed by RIA. Basal levels of PGE2 and 6-keto-PGF1 alpha were not reduced by the drug while basal TXB2 levels were lowered. However, the increased production due to HT of all PGs, was inhibited by OKY-046, especially that of TXB2. The ratio of TXB2/6-keto-PGF1 alpha, known to affect vascular tone, was reduced by OKY-046 treatment as a result of TXA2 synthesis inhibition. Still, no effect was found on the neurological outcome (as evaluated by the NSS), or on edema formation (expressed by reduced SG). Thus, based on the present findings increased TXA2 synthesis cannot be implicated in the pathophysiology of cerebral edema or dysfunction following HT.
authors.affiliation: Intensive Care Unit, Dept. of Anesthesiology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Shapira
authors.forename: G
authors.initials: G
authors.lastname: Yadid
authors.forename: S
authors.initials: S
authors.lastname: Cotev
authors.forename: E
authors.initials: E
authors.lastname: Shohami
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D015232:Dinoprostone / Q000378:metabolism; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D051381:Rats; D013046:Specific Gravity; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
chemical_list: D000179:Acrylates; D008689:Methacrylates; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase; D015232:Dinoprostone; C034364:ozagrel