Magnesium prevents seizure-induced reduction in excitatory amino acid receptor (kainate and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) binding in pregnant rat brain

Abstract

Objective: Our purpose was to evaluate the effect of seizures on kainate and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor binding in maternal rat brain and whether maternal peripheral administration of magnesium sulfate can decrease this effect. Study Design: Rats were implanted with a bipolar electrode into the hippocampus. One week of recovery was allowed before breeding. Pregnant rats were randomly assigned to 1 of 4 groups, as follows: group 1, sodium chloride and no seizures (n = 5); group 2, magnesium sulfate and no seizures (n = 4); group 3, sodium chloride and seizures (n = 8); and group 4, magnesium sulfate and seizures (n = 9). Doses of sodium chloride or magnesium sulfate were administered every 20 minutes for 4 hours to all rats on gestational days 9, 11, 13, 15, 17, and 19, followed by seizure induction (groups 3 and 4). On gestational day 20, rats were perfused, brains were dissected, and cryostat sections were taken, labeled in vitro, and placed on Hyperfilm for 4 weeks. The ligands used included kainate receptor agonist and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor agonist and antagonist. Optical density measurements of binding in 15 brain regions on each section were evaluated by 1- and 2-way analysis of variance. Results: Seizure activity was associated with decreased α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor binding of its agonist in pregnant rat brains (seizure effect, 25.9 ± 3.2 and 92.6 ± 3.4 fmol/mg tissue in hindbrain and forebrain, respectively; no seizure effect, 44.5 ± 4.7 and 110.7 ± 5.0 fmol/mg tissue in hindbrain and forebrain, respectively; P < .01). Magnesium administration was associated with increased binding of tritiated α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (magnesium effect, 44.9 ± 4.2 and 110.4 ± 4.5 fmol/mg tissue in hindbrain and forebrain, respectively; sodium chloride effect, 25.5 ± 3.7 and 92.9 ± 4.0 fmol/mg tissue in hindbrain and forebrain, respectively; P < .01). The same trend was seen with the kainate receptor in the hippocampus and hypothalamus, with a significant interaction effect between seizure and magnesium ( P < .05). Conclusions: The mechanism for maternal rat brain injury resulting from seizure activity may be, at least in part, associated with alteration in the function of excitatory amino acid receptors. Administration of magnesium sulfate can counteract this effect and may reduce resultant maternal brain damage. (Am J Obstet Gynecol 2000;183:793-8.)