Eclampsia is diagnosed in preeclamptic patients who develop unexplained
seizures and/or
coma during pregnancy or postpartum.
Eclampsia is one of the leading causes of maternal and infant morbidity and mortality, accounting for ~13% of
maternal deaths worldwide. Little is known about the mechanisms contributing to the pathophysiology of
eclampsia, partly due to the lack of suitable animal models. This study tested the hypothesis that placental
ischemia, induced by reducing utero-placental perfusion, increases susceptibility to
seizures, cerebrospinal fluid (CSF)
inflammation, and
neurokinin B (NKB) expression in brain and plasma.
Pentylenetetrazol (PTZ), a pro-convulsive
drug, was injected into pregnant and placental ischemic rats (40 mg/kg, i.p.) on gestational day 19 followed by video monitoring for 30 min. Seizure scoring was blindly conducted. Placental
ischemia hastened the onset of
seizures compared to pregnant controls but had no effect on seizure duration. Placental
ischemia increased CSF levels of
IL-2,
IL-17,
IL-18 and eotaxin (CCL11), had no effect on plasma NKB; however, PTZ increased plasma NKB in both pregnant and placental ischemic rats. NKB was strongly correlated with latency to seizure in normal pregnant rats (R(2) = 0.88 vs. 0.02 in placental ischemic rats). Lastly, NKB decreased in the anterior cerebrum in response to placental
ischemia and PTZ treatment but was unchanged in the posterior cerebrum. These data demonstrate that placental
ischemia is associated with increased susceptibility to
seizures and CSF
inflammation; thus provides an excellent model for elucidating mechanisms of
eclampsia-like symptoms. Further studies are required to determine the role of CSF
cytokines/
chemokines in mediating increased seizure susceptibility.