Eclampsia is a hypertensive disorder of pregnancy that is defined by the new onset of grand mal seizures on the basis of preeclampsia and a leading cause of maternal and fetal mortality worldwide. Presently, magnesium sulfate (MgSO) is the most effective treatment, but the mechanism by which MgSO prevents eclampsia has yet to be fully elucidated. We previously showed that systemic inflammation decreases the seizure threshold in a rat eclampsia-like model, and MgSO treatment can decrease systemic inflammation. Here, we hypothesized that MgSO plays a neuroprotective role in eclampsia by reducing neuroinflammation and brain edema. Pregnant Sprague-Dawley rats were given an intraperitoneal injection of pentylenetetrazol following a tail vein injection of lipopolysaccharide to establish the eclampsia-like seizure model. Seizure activity was assessed by behavioral testing. Neuronal loss in the hippocampal CA1 region (CA1) was detected by Nissl staining. Cerebrospinal fluid levels of S100-B and ferritin, indicators of neuroinflammation, were detected by enzyme-linked immunosorbent assay, and ionized calcium binder adapter molecule 1 (Iba-1, a marker for microglia) and glial fibrillary acid protein (GFAP, a marker for astrocytes) expression in the CA1 area was determined by immunofluorescence staining. Brain edema was measured. Our results revealed that MgSO effectively attenuated seizure severity and CA1 neuronal loss. In addition, MgSO significantly reduced cerebrospinal fluid levels of S100-B and ferritin, Iba-1 and GFAP activation in the CA1 area, and brain edema. Our results indicate that MgSO plays a neuroprotective role against eclampsia-like seizure by reducing neuroinflammation and brain edema.

Maternal-fetal fluid balance is critical during pregnancy, and amniotic fluid is essential for fetal growth and development. The placenta plays a key role in a successful pregnancy as the interface between the mother and her fetus. Aquaporins (AQPs) form specific water channels that allow the rapid transcellular movement of water in response to osmotic/hydrostatic pressure gradients. AQPs expression in the placenta and fetal membranes may play important roles in the maternal-fetal fluid balance.

ObjectiveEclampsia is a poorly understood but potentially fatal complication of pregnancy. Research to date on this disorder has been hampered by the lack of a suitable animal model. To correct this deficiency, this report describes the generation of a rat eclampsia-like model using pentylenetetrazol (PTZ) in a previously established rat preeclampsia model.MethodRats were administered lipopolysaccharide (1.0 µg/kg) by tail vein injection on gestational day 14 to establish preeclampsia (PE). PE and control rats (non-pregnant, NP; normal-pregnant, P) were injected intraperitoneally (i.p.) with PTZ (40 mg/kg) to induce seizures. In separate experiments, MgSO4 (270 mg/kg IP) was injected in advance of PTZ into PE rats to observe its effect on PTZ-induced seizures.ResultsPE conditions were verified in rats after LPS administration by significantly higher blood pressure (P<0.01) and urinary albumin excretion (P<0.05), elevated sFlt-1 (P<0.05) and decreased PlGF serum levels (P<0.05), and evidence of hepatic dysfunction compared to control groups. PTZ successfully induced seizure activity in all groups studied. Latency to seizure was significantly (P<0.01) less in the PE-PTZ group (73.2±6.6 sec.) than in PTZ-treated controls (107.0±7.4 sec.). Pretreatment with MgSO4 prolonged (P<0.05) latency to seizure, shortened seizure duration and decreased seizure rates. Significant increased (P<0.05) in the serum levels of the inflammatory cytokines TNF-α and IL-1β in PE and PE-PTZ groups, and decreased (P<0.05) in their levels following MgSO4 administration.ConclusionThis PTZ-induced eclampsia-like rat model is comparable to the human condition of eclampsia and may serve as a useful research tool for future studies of this disease. The increased inflammatory cytokines in preeclampsia are coincident with a decreased threshold for PTZ-induced seizures, suggesting that an inflammatory mechanism may contribute to the susceptibility to seizure activity and inflammation might have an important role in eclampsia.