Vezzani Annamaria, Granata Tiziana
Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Epilepsia. 2005 Nov;46(11):1724-43. doi: 10.1111/j.1528-1167.2005.00298.x.
Inflammatory reactions occur in the brain in various CNS diseases, including autoimmune, neurodegenerative, and epileptic disorders. Proinflammatory and antiinflammatory cytokines and related molecules have been described in CNS and plasma, in experimental models of seizures and in clinical cases of epilepsy. Inflammation involves both the innate and the adaptive immune systems and shares molecules and pathways also activated by systemic infection. Experimental studies in rodents show that inflammatory reactions in the brain can enhance neuronal excitability, impair cell survival, and increase the permeability of the blood-brain barrier to blood-borne molecules and cells. Moreover, some antiinflammatory treatments reduce seizures in experimental models and, in some instances, in clinical cases of epilepsy. However, inflammatory reactions in brain also can be beneficial, depending on the tissue microenvironment, the inflammatory mediators produced in injured tissue, the functional status of the target cells, and the length of time the tissue is exposed to inflammation. We provide an overview of the current knowledge in this field and attempt to bridge experimental and clinical evidence to discuss critically the possibility that inflammation may be a common factor contributing, or predisposing, to the occurrence of seizures and cell death, in various forms of epilepsy of different etiologies. The elucidation of this aspect may open new perspectives for the pharmacologic treatment of seizures.
在包括自身免疫性疾病、神经退行性疾病和癫痫症等多种中枢神经系统疾病中，大脑会发生炎症反应。在癫痫发作的实验模型以及癫痫临床病例中，中枢神经系统和血浆中均已发现促炎和抗炎细胞因子及相关分子。炎症涉及先天性和适应性免疫系统，并且共享一些也会被全身感染激活的分子和信号通路。对啮齿动物的实验研究表明，大脑中的炎症反应可增强神经元兴奋性、损害细胞存活，并增加血脑屏障对血源分子和细胞的通透性。此外，一些抗炎治疗可减少实验模型中的癫痫发作，在某些情况下，还可减少癫痫临床病例中的发作。然而，根据组织微环境、损伤组织中产生的炎症介质、靶细胞的功能状态以及组织暴露于炎症的时间长短，大脑中的炎症反应也可能是有益的。我们概述了该领域的现有知识，并试图将实验证据和临床证据联系起来，以批判性地讨论炎症可能是导致不同病因的各种形式癫痫发作和细胞死亡的共同因素或易感因素的可能性。对这一方面的阐明可能为癫痫的药物治疗开辟新的前景。
