g(m3)-ganglioside and Ischemia

The ability of brain preparations from 20-day-old rat fetuses to synthesize prostanoids in vitro before and after interruption of the maternal-fetal blood flow was examined using a radioimmunoassay technique. Synthesis of thromboxane B2 (TxB; the stable thromboxane A2 metabolite) decreased with increasing restriction time; conversely, it was elevated with reperfusion. Synthesis of 6-keto prostaglandin F1 alpha (PGF; the stable prostacyclin metabolite) and prostaglandin E2 (PGE) prostanoids remained unchanged after 20 min restriction and through a 2 hr reperfusion period. Intraperitoneal administration of GM1 (45 mg/kg) into the pregnant rat, 3 hr before restriction, stimulated synthesis of PGE and reduced synthesis of TxB. A prostanoid vasoactive index (PVI), which reflects the relative proportion of the three prostanoids synthesized and asserts the vasoactive potential of the brain tissue, was established. A rise in this value was attained after intrafetal administration into the peritoneal cavity of either GM1, GM3, or isopropyl-GM1 (AGF44) gangliosides, each given at 40 micrograms dose in 5 microliters volume, and N-dichloroacetyl-sphingosine (LIGA20; 15 micrograms/5 microliters) ganglioside analog, 1 hr before restriction. The effect was primarily due to an increase in the capacity of fetal brain tissue to synthesize PGE and, to a lesser extent PGF, vasodilating prostanoids. The N-methyl-D-aspartate (NMDA) receptor-blocker MK801 (6.6 micrograms/2 microliters) and the platelet activating factor (PAF) receptor antagonist BN52021 (0.1 mumol/2 microliters), given by the same route, effectively raised by 60-80% the vasodilating potential of the brain tissue following ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain; Dinoprostone; Dizocilpine Maleate; Female; Fetus; G(M1) Ganglioside; G(M3) Ganglioside; Gangliosides; Ischemia; Pregnancy; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Reperfusion; Thromboxane B2