Fetal rat brain damage caused by maternal seizure activity: Prevention by magnesium sulfate

Objective: Our purpose was to determine whether maternal rat seizure activity was associated with fetal histopathologic brain changes and whether magnesium sulfate reduced these changes. Study Design: Electrodes were stereotaxically implanted into the hippocampus of nonpregnant rats 1 week before breeding. Pregnant rats were randomly assigned to 1 of 4 groups: (1) sodium chloride solution and no seizure (n = 2), (2) magnesium sulfate and no seizure (n = 2), (3) sodium chloride solution and seizure (n = 5), and (4) magnesium sulfate and seizure (n = 5). On gestational days 9, 11, 13, 15, 17, and 19, subcutaneous doses of sodium chloride solution or magnesium sulfate were administered to all rats every 20 minutes for 4 hours (loading-maintenance-loading), followed by seizure induction. On gestational day 20, the rats were perfused with formalin and fetuses were delivered via cesarean. Fetuses were perfused with formalin, brains were obtained and embedded in paraffin, and the forebrain and hindbrain were sectioned in the coronal plane and stained with hematoxylin and eosin. A neuropathologist masked to the protocol performed histopathologic grading of each section, including extent and nature of cellular damage. Eleven brain regions were examined in each section. Scores were expressed as mean ± SD. Kruskal-Wallis analysis of variance was used, and P< .05 was considered significant. Results: We evaluated 26 fetal brains in group 1, 9 in group 2, 72 in group 3, and 45 in group 4. Fetuses in the sodium chloride solution–and–seizure group (group 3) presented significantly higher grades of neuronal damage in the hippocampus (group 1, 0.50 ± 0.88; group 2, 0.22 ± 0.66; group 3, 1.01 ± 1.17; and group 4, 0.48 ± 0.72) and in the tegmentum region (group 1, 1.0 ± 1.0; group 2, 0.8 ± 1.0; group 3, 1.7 ± 0.7; and group 4, 1.5 ± 0.8) (P< .05, group 3 compared with others). Isolated and patchy neuronal injury with shrinkage of cells, nuclear pyknosis, and karyorrhexis were the main histologic findings. Conclusions: Maternal rat seizure activity was associated with histologic brain injury in the fetus. Maternal administration of magnesium sulfate before seizure prevented or significantly decreased this effect. (Am J Obstet Gynecol 1999;181:828-34.)