GANGLIOSIDES STIMULATE SYNTHESIS OF PROSTAGLANDIN-E(2) AND PROSTACYCLIN IN FETAL-RAT BRAIN HEMISPHERES AFTER EPISODES OF GLOBAL INTRAUTERINE ISCHEMIA

The ability of brain preparations from 20-day-old rat fetuses to synth esize prostanoids in vitro before and after interruption of the matern al-fetal blood flow was examined using a radioimmunoassay technique. S ynthesis of thromboxane B2 (TxB; the stable thromboxane A2 metabolite) decreased with increasing restriction time; conversely, it was elevat ed with reperfusion. Synthesis of 6-keto prostaglandin F1alpha (PGF; t he stable prostacyclin metabolite) and prostaglandin E2 (PGE) prostano ids remained unchanged after 20 min restriction and through a 2 hr rep erfusion period. Intraperitoneal administration of GM1 (45 mg/kg) into the pregnant rat, 3 hr before restriction, stimulated synthesis of PG E and reduced synthesis of TxB. A prostanoid vasoactive index (PVI), w hich reflects the relative proportion of the three prostanoids synthes ized and asserts the vasoactive potential of the brain tissue, was est ablished. A rise in this value was attained after intrafetal administr ation into the peritoneal cavity of either GM1, GM3, or isopropyl-GM1 AGF44) gangliosides, each given at 40 mug dose in 5 mul volume, and N- dichloroacetyl-sphingosine (LIGA20; 15 mug/5 mul) ganglioside analog, 1 hr before restriction. The effect was primarily due to an increase i n the capacity of fetal brain tissue to synthesize PGE and, to a lesse r extent PGF, vasodilating prostanoids. The N-methyl-D-aspartate (NMDA ) receptor blocker MK801 (16.6 mug/2 mul) and the platelet activating factor (PAF) receptor antagonist BN52021 (0.1 mumol/2 mul), given by t he same route, effectively raised by 60-80% the vasodilating potential of the brain tissue following ischemia. Based on the commonality seen with these chemically diverse anti-ischemic agents, it is hypothesize d that PGE and PGF elevation by gangliosides may be beneficial rather than detrimental for the fetal ischemic brain. (C) 1993 Wiley-Liss, In c.