Pro-epileptogenic effects of viral-like inflammation in both mature and immature brains.
Pro-epileptogenic effects of viral-like inflammation in both mature and immature brains.
复制标题
病毒样炎症在成熟和未成熟大脑中的促发作性作用。
DOI：
10.1186/s12974-016-0773-6
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发表时间：
2016-12-12
影响因子：
9.3
通讯作者：
Auvin S
中科院分区：
文献类型：
--
作者：
Dupuis N;Mazarati A;Desnous B;Chhor V;Fleiss B;Le Charpentier T;Lebon S;Csaba Z;Gressens P;Dournaud P;Auvin S
感染性脑碱最常与感染期间的急性癫痫发作有关，并且是以后发展为癫痫的危险因素。病毒性脑炎诱发癫痫发生的机制尚不清楚。在这里，我们评估了病毒性脑炎相关炎症对大鼠icogenesis和癫痫发生的贡献，使用快速点燃方案。此外，我们还研究了米诺环素是否可以改善病毒性脑炎症的预后。为了产生病毒样炎症，将toll样受体3 （TLR3）激动剂多肌苷-多胞酸（PIC）应用于小胶质/巨噬细胞培养以及出生后第13天（P13）和出生后第74天（P74）大鼠的海马。细胞培养允许检查PIC诱导的炎症，而体内设置更适合分析细胞因子产生和炎症对癫痫发生的影响。在点火前连续3天腹腔注射米诺环素（50 mg/kg），以评估其对炎症和癫痫发生的影响。PIC注射促进了点燃癫痫发生，这在两个年龄阶段的完全边缘癫痫发作数量的增加中是明显的。此外，在P14大鼠中，我们观察到癫痫发作更快，点火状态保持时间更长。PIC也导致P14和P75大鼠海马中白细胞介素1β (IL-1β)水平升高。在P14和P75大鼠中，二甲胺四环素治疗既不能逆转PIC的致痫作用，也不能逆转海马中IL-1β的增加。海马注射PIC促进了P14和P75的快速癫痫发生，这表明病毒诱导的炎症增加了癫痫发生，而与脑成熟无关。然而，二甲胺四环素不能逆转癫痫发生的增加，这可能与它对两个年龄的海马IL-1β水平没有影响有关。本文的在线版本（doi:10.1186/s12974-016-0773-6）包含补充材料，可供授权用户使用。
Infectious encephalitides are most often associated with acute seizures during the infection period and are risk factors for the development of epilepsy at later times. Mechanisms of viral encephalitis-induced epileptogenesis are poorly understood. Here, we evaluated the contribution of viral encephalitis-associated inflammation to ictogenesis and epileptogenesis using a rapid kindling protocol in rats. In addition, we examined whether minocycline can improve outcomes of viral-like brain inflammation. To produce viral-like inflammation, polyinosinic-polycytidylic acid (PIC), a toll-like receptor 3 (TLR3) agonist, was applied to microglial/macrophage cell cultures and to the hippocampus of postnatal day 13 (P13) and postnatal day 74 (P74) rats. Cell cultures permit the examination of the inflammation induced by PIC, while the in vivo setting better suits the analysis of cytokine production and the effects of inflammation on epileptogenesis. Minocycline (50 mg/kg) was injected intraperitoneally for 3 consecutive days prior to the kindling procedure to evaluate its effects on inflammation and epileptogenesis. PIC injection facilitated kindling epileptogenesis, which was evident as an increase in the number of full limbic seizures at both ages. Furthermore, in P14 rats, we observed a faster seizure onset and prolonged retention of the kindling state. PIC administration also led to an increase in interleukin 1β (IL-1β) levels in the hippocampus in P14 and P75 rats. Treatment with minocycline reversed neither the pro-epileptogenic effects of PIC nor the increase of IL-1β in the hippocampus in both P14 and P75 rats. Hippocampal injection of PIC facilitates rapid kindling epileptogenesis at both P14 and P75, suggesting that viral–induced inflammation increases epileptogenesis irrespective of brain maturation. Minocycline, however, was unable to reverse the increase of epileptogenesis, which might be linked to its absence of effect on hippocampal IL-1β levels at both ages. The online version of this article (doi:10.1186/s12974-016-0773-6) contains supplementary material, which is available to authorized users.
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4.8
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