Abstract

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.

Highlights

  • Significant increased (P,0.05) in the serum levels of the inflammatory cytokines TNF-a and IL-1b in PE and PE-PTZ groups, and decreased (P,0.05) in their levels following MgSO4 administration. This 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

  • Eclampsia is characterized by grand mal seizures that cannot be attributed to other causes in women with the human pregnancyspecific disorder preeclampsia

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Summary

Introduction

Eclampsia is characterized by grand mal seizures that cannot be attributed to other causes in women with the human pregnancyspecific disorder preeclampsia. The clinical manifestations of maternal preeclampsia are hypertension and proteinuria with or without coexisting systemic abnormalities involving the kidneys, liver, or blood. There is a fetal manifestation of preeclampsia involving fetal growth restriction, reduced amniotic fluid, and abnormal fetal oxygenation [1]. Eclampsia manifests as one or more grand mal seizures. Eclampsia is estimated to complicate 1.4% of all deliveries [2]. Maternal deaths from eclampsia are rare, but in developing countries the mortality rate can be as high as 15% [3]

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