Immune mechanisms in epileptogenesis.
Immune mechanisms in epileptogenesis.
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DOI：
10.3389/fncel.2013.00195
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发表时间：
2013
影响因子：
5.3
通讯作者：
Koh S
中科院分区：
文献类型：
--
作者：
Xu D;Miller SD;Koh S
癫痫是一种慢性脑部疾病，影响全球1%的人口。免疫应答与癫痫发作诱导和癫痫的发展有关。临床前和临床证据已经积累，表明脑炎症和癫痫发生之间存在正反馈循环。长期或复发性癫痫发作和脑损伤导致促炎细胞因子的上调和激活的免疫应答，以进一步增加癫痫发作易感性，促进神经元兴奋性，并诱导血脑屏障破坏。本文就先天免疫和适应性免疫在癫痫发病机制中的作用作一综述。人类研究和动物模型，有助于描绘癫痫发生脑炎症的贡献将进行讨论。我们强调了脑驻留免疫介质的关键作用，并强调脑浸润外周血白细胞的贡献。此外，我们提出了癫痫发生的可能免疫机制。几个促炎途径进行了讨论，包括白细胞介素-1受体/Toll样受体信号级联，损伤相关的分子模式激活的途径，环氧合酶-2/前列腺素途径。最后，考虑开发针对这些机制中确定的关键成分和过程的更好的疗法，例如，以抗原特异性方式有效阻断这些途径的工程拮抗剂。
Epilepsy is a chronic brain disorder that affects 1% of the human population worldwide. Immune responses are implicated in seizure induction and the development of epilepsy. Pre-clinical and clinical evidence have accumulated to suggest a positive feedback cycle between brain inflammation and epileptogenesis. Prolonged or recurrent seizures and brain injuries lead to upregulation of proinflammatory cytokines and activated immune responses to further increase seizure susceptibility, promote neuronal excitability, and induce blood–brain barrier breakdown. This review focuses on the potential role of innate and adaptive immune responses in the pathogenesis of epilepsy. Both human studies and animal models that help delineate the contributions of brain inflammation in epileptogenesis will be discussed. We highlight the critical role of brain-resident immune mediators and emphasize the contribution of brain-infiltrating peripheral leukocytes. Additionally, we propose possible immune mechanisms that underlie epileptogenesis. Several proinflammatory pathways are discussed, including the interleukin-1 receptor/toll-like receptor signaling cascade, the pathways activated by damage-associated molecular patterns, and the cyclooxygenase-2/prostaglandin pathway. Finally, development of better therapies that target the key constituents and processes identified in these mechanisms are considered, for instance, engineering antagonizing agents that effectively block these pathways in an antigen-specific manner.
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DOI：
10.1016/j.jpeds.2012.10.011
发表时间：
2013-04
期刊：
The Journal of pediatrics
影响因子：
--
作者：
Armangue T;Titulaer MJ;Málaga I;Bataller L;Gabilondo I;Graus F;Dalmau J;Spanish Anti-N-methyl-D-Aspartate Receptor (NMDAR) Encephalitis Work Group
通讯作者：
Spanish Anti-N-methyl-D-Aspartate Receptor (NMDAR) Encephalitis Work Group
影响因子：
11.2
作者：
Bauer, Jan;Eiger, Christian E.;Bien, Christian G.
通讯作者：
Bien, Christian G.
影响因子：
2.2
作者：
Boer, K.;Jansen, F.;Aronica, E.
通讯作者：
Aronica, E.
DOI：
10.1007/bf01179819
发表时间：
1995-09-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
BELL, MD;PERRY, VH
通讯作者：
PERRY, VH
影响因子：
4.4
作者：
CUTLER, RWP;WATTERS, GV;HAMMERSTAD, JP
通讯作者：
HAMMERSTAD, JP