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

OBJECTIVE: Our purpose was to determine whether maternal rat seizure activi ty was associated with fetal histopathologic brain changes and whether magn esium sulfate reduced these changes. STUDY DESIGN: Electrodes were stereotaxically implanted into the hippocampu s of nonpregnant rats I week before breeding. Pregnant rats were randomly a ssigned 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 solut ion 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 ch loride solution or magnesium sulfate were administered to all rats every 20 minutes for 4 hours (loading-maintenance-loading), followed by seizure ind uction. On gestational day 20, the rats were perfused with formalin and fet uses were delivered via cesarean. Fetuses were perfused with formalin, brai ns 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 gradin g of each section, including extent and nature of cellular damage. Eleven b rain regions were examined in each section. Scores were expressed as mean /- SD. Kruskal-Wallis analysis of Variance was used, and P < .05 was consid ered 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 (gro up 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 b rain injury in the fetus. Maternal administration of magnesium sulfate befo re seizure prevented or significantly decreased this effect.