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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-PGF1α 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-PGF1α 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
, 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.

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References
- Current concepts of the role of prostaglandins and other eicosanoids in acute cerebrovascular disease.in: Mackenzie ET L.E.R.S.vol. 2. Raven Press, New York1984: 191-218
- Prostaglandin endoperoxides — novel transformation of arachidonic acid in human platelets.in: Proc Natl Acad Sci (USA). 71. 1974: 3400-3404
- Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2 and prostacyclin.Pharmacol Rev. 1979; 30: 293-331
- Vasodilator prostaglandins (PG) prevent renal damage after ischemia.Ann Surg. 1987; 205: 195-198
- Prostaglandin I2 and indomethacin prevent impairment of post-ischemic brain reperfusion in the dog.Stroke. 1979; 10: 629-637
- Antihypoxic effect of prostacyclin.Meth Find Exptl Clin Pharmacol. 1982; 4: 211-219
- Anti-hypoxic effect of centrally and systemically administration of prostacyclin (PGI2).Meth Find Exptl Clin Pharmacol. 1984; 6: 691-693
- Modification of focal cerebral ischemia by prostacyclin and indomethacin.J Neurosurg. 1983; 58 (1983): 714-719
- Protective effect of a new prostacyclin analogue OP-2507 against cerebral anoxia and edema in experimental animals.Eur J Pharmacol. 1986; 123: 335-344
- Protective effect of prostaglandins D2, E1 and I2 against cerebral hypoxia/anoxia in mice.Naunyn-Schmiedeberg's Arch Pharmacol. 1986; 334: 282-289
- Anti ischemic actions of a new thromboxane receptor antagonist, SQ-29548, in acute myocardial ischemia.Eur J Pharmacol. 1986; 122: 213-219
- Treatment of experimental cerebral ischemia.J Cereb Blood Flow Metabol. 1982; 2: 275-297
- Arachidonate-induced cerebrovascular occlusion in the rat. The role of platelets and aspirin in stroke.Neurology (Minneap). 1976; 26: 297-304
- Recovery from global cerebral ischemia in rabbits: influence of indomethacin.Eur Neurol. 1981; 20: 230-234
- Cerebral platelet thromboembolism and thromboxane synthetase inhibition.Stroke. 1985; 16: 800-805
- Head injury induces increased prostaglandin synthesis in rat brain.J Cereb Blood Flow Metab. 1987; 7: 58-63
- Experimental closed head injury in rats: Prostaglandins production in a non-injured zone.Neurosurg. 1988; (in press)
- Dexamethasone and indomethacin do not affect brain edema following head injury in rats.J Cereb Blood Flow Metabol. 1988; (in press)
- Experimental closed head injury in rats: mechanical, pathophysiological and neurological properties.Crit Care Med. 1988; 16: 258-265
- An improved gravimetric measure of cerebral edema.J Neurosurg. 1982; 56: 246-253
- Use of specific gravity in the measurement of cerebral edema.J Appl Physiol. 1971; 30: 268-271
- The effect of incomplete cerebral ischemia on prostaglandin levels in rat brain.Stroke. 1982; 13: 494-498
- Protein measurement with the folin phenol reagent.J Biol Chem. 1951; 193: 265-275
- An ex vivo method for evaluating prostaglandin synthetase activity in cortical slices of mouse brain.J Neurochem. 1985; 45: 132-136
- Increased thromboxane and 5-HETE production following spinal cord ischemia in the rabbit.Prostaglandins Leukotrienes and Medicine. 1987; 28: 169-181
- Development of cyclooxygenase and lipoxygenase metabolites of arachidonic acid after transient cerebral ischemia.J Neurosurg. 1986; 64: 118-124
- Thromboxane synthetase inhibition with imidazole increases blood flow in ischemic penumbra. 1988; 22: 317-323
- Effect of thromboxane synthetase inhibitors (OKY-046, OKY-1580) on experimentally induced air embolism in anesthetized dogs.Prostaglandins Leukotrienes and Medicine. 1986; 21: 197-206
- Clinical study on effect of thromboxane A2 synthetase inhibitor (OKY-046) to clarify the regulation of cerebral blood flow in cerebral thrombosis.in: 6th International Conference on Prostaglandins and related compounds, Florence, Italy1986: 410
- The effects of verapamil, thromboxane synthetase inhibitor, chlorpromazine and propranolol in acute focal cerebral ischemia.J Cerebr Blood Flow Metabol. 1983; 3: S367-S368
- Prostacyclin and thromboxane A2 moderate post ischemic renal failure.Surgery. 1985; 98: 207-212
- Effect of a stable prostacyclin analogue on canine renal allograft rejection.Ann Surg. 1987; 205: 199-202
- Protective actions of a new thromboxane synthetase inhibitor in arachidonate induced sudden death.Life Sci. 1984; 35: 1763-1768
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© 1989 Published by Elsevier Inc.