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

Decreased seizure threshold in an eclampsia-like model induced in pregnant rats with lipopolysaccharide and pentylenetetrazol treatments.
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脂多糖和戊四唑治疗可降低妊娠大鼠子痫样模型中的癫痫阈值

DOI:
10.1371/journal.pone.0089333
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Liu H
Liu H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Huang Q;Liu L;Hu B;Di X;Brennecke SP;Liu H

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目的子痫是一种鲜为人知但可能致命的妊娠并发症。迄今为止,由于缺乏合适的动物模型,对这种疾病的研究一直受到阻碍。为了纠正这一缺陷,本报告描述了在先前建立的大鼠子痫前期模型中使用戊四唑(PTZ)产生大鼠子痫样模型。方法妊娠第14天尾静脉注射脂多糖1.0µg/kg,建立子痫前期(PE)。PE和对照大鼠(未妊娠,NP;正常妊娠,P)腹腔注射PTZ (40 mg/kg)诱导癫痫发作。在单独实验中,在PTZ前给PE大鼠注射MgSO4 (270 mg/kg IP),观察其对PTZ诱导癫痫发作的影响。结果与对照组相比,LPS给药后大鼠血压(P<0.01)、尿白蛋白排泄(P<0.05)、血清sFlt-1升高(P<0.05)、PlGF水平降低(P<0.05),并出现肝功能障碍。PTZ成功地诱导了所有实验组的癫痫发作活动。PE-PTZ组癫痫发作潜伏期(73.2±6.6秒)明显低于ptz组(107.0±7.4秒)。MgSO4预处理延长了癫痫发作潜伏期(P<0.05),缩短了癫痫发作时间,降低了癫痫发作率。PE组和PE- ptz组血清炎症因子TNF-α和IL-1β水平显著升高(P<0.05), MgSO4组血清炎症因子TNF-α和IL-1β水平显著降低(P<0.05)。结论ptz诱导的子痫样大鼠模型与人子痫相似,可为子痫的进一步研究提供有益的工具。子痫前期炎症细胞因子的增加与ptz诱发的癫痫发作阈值的降低是一致的,这表明炎症机制可能有助于癫痫发作活动的易感性,炎症可能在子痫中起重要作用。
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 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. Conclusion 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.
DOI: 10.1016/j.expneurol.2012.01.005
发表时间: 2012-04
影响因子: 5.3
作者:
Cipolla, Marilyn J.;Pusic, Aya D.;Grinberg, Yelena Y.;Chapman, Abbie C.;Poynter, Matthew E.;Kraig, Richard P.
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发表时间: 2012-06-01
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DOI: 10.1089/jir.2012.0013
发表时间: 2012-09-01
影响因子: 2.3
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DOI: 10.1016/s0002-9378(12)90855-8
发表时间: 1993-03-01
影响因子: 9.8
作者:
COTTON, DB;HALLAK, M;BERMAN, RF
通讯作者: BERMAN, RF