Neuroinflammatory targets and treatments for epilepsy validated in experimental models.
Neuroinflammatory targets and treatments for epilepsy validated in experimental models.
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DOI：
10.1111/epi.13783
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发表时间：
2017-07
期刊：
影响因子：
5.6
通讯作者：
Kaminski RM
中科院分区：
文献类型：
--
作者：
Aronica E;Bauer S;Bozzi Y;Caleo M;Dingledine R;Gorter JA;Henshall DC;Kaufer D;Koh S;Löscher W;Louboutin JP;Mishto M;Norwood BA;Palma E;Poulter MO;Terrone G;Vezzani A;Kaminski RM
过去十年积累的大量证据有力地支持了炎症在人类癫痫的病理生理学中的作用。在不同的癫痫实验模型中，已经确定了影响不同病理结果的特定炎症分子和途径。最重要的是，在手术切除的难治性癫痫患者的脑组织中也发现了同样的炎症途径。从这些新的潜在靶点可能衍生出新的抗癫痫疗法。一个基本而关键的问题是，靶向这些分子和途径是否会导致抗细胞分裂、抗癫痫和/或疾病修饰的效果。因此，需要在模拟癫痫发生的相关方面的模型中进行临床前测试，以指导综合实验和临床试验设计。我们讨论了最新的临床前概念验证研究，在动物模型中验证了一些针对炎症机制的治疗方法，这些方法可能代表癫痫药物开发的新途径。最后，我们建议未来的方向，以加快这些最新发现的临床前到临床的转化。
A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New anti-seizure therapies may be derived from these novel potential targets. An essential and crucial question is whether targeting these molecules and pathways may result in anti-ictogenesis, anti-epileptogenesis and/or disease-modification effects. Therefore, preclinical testing in models mimicking relevant aspects of epileptogenesis is needed to guide integrated experimental and clinical trial designs. We discuss the most recent preclinical proof-of-concept studies validating a number of therapeutic approaches against inflammatory mechanisms in animal models that could represent novel avenues for drug development in epilepsy. Finally, we suggest future directions to accelerate preclinical to clinical translation of these recent discoveries.
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