title: Decreased seizure threshold in an eclampsia-like model induced in pregnant rats with lipopolysaccharide and pentylenetetrazol treatments.
abstract: OBJECTIVE
  Eclampsia 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.
  
  
  METHODS
  Rats 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.
  
  
  RESULTS
  PE 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
authors.forename: Bihui
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China ; School of Medicine, Jinan University, Guangzhou, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Di
authors.affiliation: Department Perinatal Medicine Pregnancy Research Centre and University of Melbourne Department of Obstetrics and Gynaecology, Royal Women's Hospital, Parkville, Victoria, Australia.
authors.forename: Shaun Patrick
authors.initials: SP
authors.lastname: Brennecke
authors.affiliation: Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
authors.forename: Huishu
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004461:Eclampsia / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008278:Magnesium Sulfate / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000633:toxicity*; D011247:Pregnancy; D011256:Pregnancy Outcome; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D008070:Lipopolysaccharides; D008278:Magnesium Sulfate; D010433:Pentylenetetrazole