The Contribution of Normal Pregnancy to Eclampsia

Eclampsia, clinically defined as unexplained seizure in a woman with preeclampsia, is a life threatening complication unique to the pregnant state. However, a subpopulation of women with seemingly uncomplicated pregnancies experience de novo seizure without preeclamptic signs or symptoms, suggesting pregnancy alone may predispose the brain to seizure. Here, we hypothesized that normal pregnancy lowers seizure threshold and investigated mechanisms by which pregnancy may affect seizure susceptibility, including neuroinflammation and plasticity of gamma-aminobutyric acid type A receptor (GABA(A)R) subunit expression. Seizure threshold was determined by quantifying the amount of pentylenetetrazole (PTZ) required to elicit electrical seizure in Sprague Dawley rats that were either nonpregnant (Nonpreg, n = 7) or pregnant (Preg; d20, n = 6). Seizure-induced vasogenic edema was also measured. Further, activation of microglia, a measure of neuroinflammation (n = 6-8/group), and GABA(A)R δ- and γ2-subunit protein expression in the cerebral cortex and hippocampus (n = 6/group) was determined. Seizure threshold was lower in Preg compared to Nonpreg rats (36.7±9.6 vs. 65.0±14.5 mg/kg PTZ; p<0.01) that was associated with greater vasogenic edema formation (78.55±0.11 vs. 78.04±0.19% water; p<0.05). The % of active microglia was similar between groups; however, pregnancy was associated with downregulation of cortical GABA(A)R-δ and hippocampal GABA(A)R-γ2 expression. Overall, pregnancy appears to be a state of increased seizure susceptibility that is not due to neuroinflammation, but rather is associated with reduced expression of GABA(A)R subunits and greater edema. Understanding neurophysiological changes occurring in normal pregnancy could allow for better prevention and management of de novo seizure, including pathologic states such as eclampsia.