Epilepsy, Seizures, and Inflammation: Role of the C-C Motif Ligand 2 Chemokine
Epilepsy, Seizures, and Inflammation: Role of the C-C Motif Ligand 2 Chemokine
复制标题
DOI：
10.1089/dna.2016.3345
复制
发表时间：
2016-06-01
影响因子：
3.1
通讯作者：
Caleo, Matteo
中科院分区：
文献类型：
--
作者：
Bozzi, Yuri;Caleo, Matteo
癫痫是一种以自发性反复发作为特征的慢性疾病。几条证据表明，脑实质内的炎症过程有助于癫痫发作的复发和沉淀。在癫痫患者和动物模型中，癫痫发作上调炎症介质，这反过来又可能增强大脑的兴奋性。我们最近发现，C-C基序配体2（CCL 2）趋化因子（也称为单核细胞趋化蛋白-1 [MCP-1]）介导炎症的促凋亡作用。慢性癫痫小鼠的全身炎症激发显著增强癫痫发作频率，并上调脑中CCL 2的表达。选择性药理学阻断CCL 2合成或C-C趋化因子受体2（CCR 2）可显著抑制炎症诱导的癫痫发作。这些结果对开发新的抗惊厥疗法具有重要意义：干扰CCL 2信号传导的药物在临床上用于治疗几种人类疾病，并可能重新定向用于耐药性癫痫。在这里，我们回顾了CCL 2/CCR 2信号在全身炎症与癫痫易感性之间的作用，并讨论了我们最近研究中出现的一些开放性问题。
Epilepsy is a chronic disorder characterized by spontaneous recurrent seizures. Several lines of evidence demonstrate that inflammatory processes within the brain parenchyma contribute to recurrence and precipitation of seizures. In both epileptic patients and animal models, seizures upregulate inflammatory mediators, which in turn may enhance brain excitability. We recently showed that the C-C motif ligand 2 (CCL2) chemokine (also known as monocyte chemoattractant protein-1 [MCP-1]) mediates the seizure-promoting effects of inflammation. Systemic inflammatory challenge in chronically epileptic mice markedly enhanced seizure frequency and upregulated CCL2 expression in the brain. Selective pharmacological blockade of CCL2 synthesis or C-C chemokine receptor type 2 (CCR2) significantly suppressed inflammation-induced seizures. These results have important implications for the development of novel anticonvulsant therapies: drugs interfering with CCL2 signaling are used clinically for several human disorders and might be redirected for use in pharmacoresistant epilepsy. Here we review the role of CCL2/CCR2 signaling in linking systemic inflammation with seizure susceptibility and discuss some open questions that arise from our recent studies.