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2015 ; 10
(7
): e0133953
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The Contribution of Normal Pregnancy to Eclampsia
#MMPMID26218425
Johnson AC
; Nagle KJ
; Tremble SM
; Cipolla MJ
PLoS One
2015[]; 10
(7
): e0133953
PMID26218425
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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 (GABAAR) 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 GABAAR ?- and
?2-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 GABAAR-? and hippocampal GABAAR-?2 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 GABAAR 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.
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