Pregnant serum induces neuroinflammation and seizure activity via TNFα.
Pregnant serum induces neuroinflammation and seizure activity via TNFα.
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DOI：
10.1016/j.expneurol.2012.01.005
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发表时间：
2012-04
影响因子：
5.3
通讯作者：
Kraig, Richard P.
中科院分区：
文献类型：
--
作者：
Cipolla, Marilyn J.;Pusic, Aya D.;Grinberg, Yelena Y.;Chapman, Abbie C.;Poynter, Matthew E.;Kraig, Richard P.
先兆子痫是一种妊娠期高血压疾病，会影响包括大脑在内的许多器官。先兆子痫期间会出现神经系统并发症，其中最严重的是癫痫发作，称为子痫。虽然子痫前期可以先于子痫发作，但它通常发生在正常妊娠期间，这表明与正常妊娠相关的过程可以促进神经元的兴奋性。在这里，我们调查了在妊娠晚期癫痫发作时升高的循环炎症介质是否对神经元组织过度兴奋。用未孕或晚孕Wistar大鼠血清替代正常生长的正常马血清48h，对海马片进行诱发电位测定。我们发现，怀孕大鼠的血清，而不是非怀孕大鼠的血清，会引起海马神经元的过度兴奋和惊厥活动，而这种活动可以通过抑制肿瘤坏死因子α信号而被取消。此外，应用肿瘤坏死因子α可模拟这种兴奋性的增加。妊娠血清还引起小胶质细胞激活的形态变化，并增加了非妊娠血清中未见的肿瘤坏死因子α基因表达。然而，妊娠血清中未发现肿瘤坏死因子α蛋白的升高，提示孕期其他循环因素可引起海马片细胞的激活，从而产生肿瘤坏死因子α介导的神经元兴奋性增加。最后，虽然怀孕血清引起了神经炎症和海马片的过度兴奋，但它没有增加血脑屏障的通透性，也没有使服用该血清的怀孕大鼠癫痫发作。因此，血脑屏障在保护大脑免受妊娠期间对大脑过度兴奋的循环神经炎性介质的影响方面具有重要作用。这些研究为无血压升高的子痫的潜在原因以及防止大脑暴露于过度兴奋因素的血脑屏障的保护作用提供了新的见解。
Preeclampsia is a hypertensive disorder of pregnancy that affects many organs including the brain. Neurological complications occur during preeclampsia, the most serious of which is seizure known as eclampsia. Although preeclampsia can precede the eclamptic seizure, it often occurs during normal pregnancy, suggesting that processes associated with normal pregnancy can promote neuronal excitability. Here we investigated whether circulating inflammatory mediators that are elevated late in gestation when seizure also occurs are hyperexcitable to neuronal tissue. Evoked field potentials were measured in hippocampal slices in which control horse serum that slices are normally grown in, was replaced with serum from nonpregnant or late-pregnant Wistar rats for 48 hours. We found that serum from pregnant, but not nonpregnant rats, caused hyperexcitability to hippocampal neurons and seizure activity that was abrogated by inhibition of tumor necrosis factor alpha (TNFα) signaling. Additionally, application of TNFα mimicked this increased excitability. Pregnant serum also caused morphological changes in microglia characteristic of activation, and increased TNFα mRNA expression that was not seen with exposure to nonpregnant serum. However, TNFα protein was not found to be elevated in pregnant serum itself, suggesting that other circulating factors during pregnancy caused activation of hippocampal slice cells to produce a TNFα-mediated increase in neuronal excitability. Lastly, although pregnant serum caused neuroinflammation and hyperexcitability of hippocampal slices, it did not increase blood-brain barrier permeability, nor were pregnant rats from which the serum was taken undergoing seizure. Thus, the BBB has an important role in protecting the brain from circulating neuroinflammatory mediators that are hyperexcitable to the brain during pregnancy. These studies provide novel insight into the underlying cause of eclampsia without elevated blood pressure and the protective role of the BBB that prevents exposure of the brain to hyperexcitable factors.
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DOI：
10.1097/00004647-199701000-00005
发表时间：
1997-01-01
影响因子：
6.3
作者：
Kunkler, PE;Kraig, RP
通讯作者：
Kraig, RP
影响因子：
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作者：
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通讯作者：
Kraig, RP
影响因子：
5.3
作者：
D'Mello, Charlotte;Le, Tai;Swain, Mark G.
通讯作者：
Swain, Mark G.
影响因子：
9.8
作者：
Katz, VL;Farmer, R;Kuller, JA
通讯作者：
Kuller, JA
影响因子：
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作者：
Ladeby, R;Wirenfeldt, M;Finsen, B
通讯作者：
Finsen, B