OKY-046 inhibits thromboxane synthesis with no effect on brain edema and neurological status in head traumatized rats

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-PGF_1α 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-PGF_1α 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-PGF_1α, 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.