Prostaglandin endoperoxide synthase-2 abundance is increased in brain tissues of late-gestation fetal sheep in response to cerebral hypoperfusion

OBJECTIVE: To determine the mechanism by which cerebral hypoperfusion enhan ces prostanoid secretion by fetal brain tissues. METHODS: Studies were preformed on five intact and five carotid sinus-dener vated sheep fetuses (124-136 days) exposed to 10 minutes of cerebral hypope rfusion. Plasma collected from lingual artery and sagittal sinus, and micro dialysates collected from brain stem and hypothalamus were assayed for pros tanoid production. Fetal hypothalamus, cerebral cortex, hippocampus, cerebe llum, and brain stem were collected from intact animals and 30 minutes afte r cerebral hypoperfusion for the expression, activity, and distribution of prostaglandin endoperoxide synthase-1 (PGHS-1), PGHS-2, and thromboxane syn thase. RESULTS: Thromboxane B-2 increased significantly in sagittal sinus compared with arterial blood, but PGE(2) did not change. Thromboxane B-2 decreased in brain stem and hypothalamus microdialysates, and prostaglandin E-2 incre ased in these regions. PGHS-2 immunoreactive protein levels in brain tissue s increased in the cerebral hypoperfusion fetuses compared with those of th e intact animals. By contrast, PGHS-1 and thromboxane synthase protein leve ls did not change between these two groups. Prostaglandin endoperoxide synt hase activity in brain tissues decreased with the increased levels of immun oreactive PGHS-2. CONCLUSIONS: 1) Prostanoids are produced in response to cerebral hypoperfus ion, 2) the increase in the production of prostanoid responses to cerebral hypoperfusion is associated with the decrease in activity of, and therefore , the "suicide" inactivation of PGHS, and 3) PGHS-2 is the predominant form of PGHS, whose synthesis is induced by cerebral hypoperfusion in the fetal brain. Copyright (C) 1999 by the Society for Gynecologic Investigation.