Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines.
Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines.
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DOI：
10.14814/phy2.12634
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发表时间：
2015-11
影响因子：
2.5
通讯作者：
Warrington JP
中科院分区：
文献类型：
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作者：
Warrington JP
子痫被诊断为先兆子痫患者谁发展不明原因的癫痫发作和/或昏迷在怀孕期间或产后。子痫是孕产妇和婴儿发病和死亡的主要原因之一，占全球孕产妇死亡的0.13%。对于子痫的病理生理机制知之甚少，部分原因是缺乏合适的动物模型。本研究验证了以下假设：通过减少子宫-胎盘灌注诱导的胎盘缺血增加了对癫痫发作、脑脊液（CSF）炎症以及脑和血浆中神经激肽B（NKB）表达的易感性。将致惊厥药戊四氮（PTZ）注射到妊娠和胎盘缺血大鼠（40 mg/kg，i. p.）在妊娠第19天，随后视频监测30分钟。癫痫发作评分采用盲法进行。与妊娠对照组相比，胎盘缺血加速癫痫发作，但对癫痫发作持续时间无影响。胎盘缺血增加了CSF中IL-2、IL-17、IL-18和嗜酸性粒细胞趋化因子（CCL 11）的水平，对血浆NKB无影响;然而，PTZ增加了妊娠和胎盘缺血大鼠的血浆NKB。NKB与正常妊娠大鼠的癫痫发作潜伏期密切相关（R2 = 0.88，胎盘缺血大鼠为0.02）。最后，NKB减少在前脑的胎盘缺血和PTZ治疗，但在后脑无变化。这些数据表明，胎盘缺血与癫痫发作和CSF炎症的易感性增加有关;因此，为阐明子痫样症状的机制提供了一个很好的模型。需要进一步研究以确定CSF细胞因子/趋化因子在介导癫痫发作易感性增加中的作用。
Eclampsia is diagnosed in preeclamptic patients who develop unexplained seizures and/or coma during pregnancy or postpartum. Eclampsia is one of the leading causes of maternal and infant morbidity and mortality, accounting for ∼13% of maternal deaths worldwide. Little is known about the mechanisms contributing to the pathophysiology of eclampsia, partly due to the lack of suitable animal models. This study tested the hypothesis that placental ischemia, induced by reducing utero-placental perfusion, increases susceptibility to seizures, cerebrospinal fluid (CSF) inflammation, and neurokinin B (NKB) expression in brain and plasma. Pentylenetetrazol (PTZ), a pro-convulsive drug, was injected into pregnant and placental ischemic rats (40 mg/kg, i.p.) on gestational day 19 followed by video monitoring for 30 min. Seizure scoring was blindly conducted. Placental ischemia hastened the onset of seizures compared to pregnant controls but had no effect on seizure duration. Placental ischemia increased CSF levels of IL-2, IL-17, IL-18 and eotaxin (CCL11), had no effect on plasma NKB; however, PTZ increased plasma NKB in both pregnant and placental ischemic rats. NKB was strongly correlated with latency to seizure in normal pregnant rats (R2 = 0.88 vs. 0.02 in placental ischemic rats). Lastly, NKB decreased in the anterior cerebrum in response to placental ischemia and PTZ treatment but was unchanged in the posterior cerebrum. These data demonstrate that placental ischemia is associated with increased susceptibility to seizures and CSF inflammation; thus provides an excellent model for elucidating mechanisms of eclampsia-like symptoms. Further studies are required to determine the role of CSF cytokines/chemokines in mediating increased seizure susceptibility.