Decreased seizure threshold in an eclampsia-like model induced in pregnant rats with lipopolysaccharide and pentylenetetrazol treatments

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. Method: Rats were administered lipopolysaccharide (1.0 mg/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 (73.266.6 sec.) than in PTZ-treated controls (107.067.4 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-a and IL-1b in PE and PE-PTZ groups, and decreased (P,0.05) in their levels following MgSO4 administration