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Gangliosides stimulate synthesis of prostaglandin E 2 and prostacyclin in fetal rat brain hemispheres after episodes of global intrauterine ischemia
Author(s) -
Yavin E.,
Gil S.,
Kunievsky B.,
Harel S.
Publication year - 1993
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490360411
Subject(s) - prostacyclin , medicine , endocrinology , prostanoid , thromboxane , prostaglandin , thromboxane a2 , chemistry , thromboxane b2 , receptor , biology , platelet
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 B 2 (TxB; the stable thromboxane A 2 metabolite) decreased with increasing restriction time; conversely, it was elevated with reperfusion. Synthesis of 6‐keto prostaglandin F 1α (PGF; the stable prostacyclin metabolite) and prostaglandin E 2 (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 40μg dose in 5 μl volume, and N‐dichloroacetyl‐sphingosine (LIGA20; 15μg/5μl) 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 μg/μl) and the platelet activating factor (PAF) receptor antagonist BN52021 (0.1μmol/2μl), given by the 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 hypothesized that PGE and PGF elevation by gangliosides may be benefical rather than detrimental for the fetal ischemic brain. © 1993 Wiley‐Liss, Inc.