Are you in or out? Leukocyte, ion, and neurotransmitter permeability across the epileptic blood-brain barrier
Are you in or out? Leukocyte, ion, and neurotransmitter permeability across the epileptic blood-brain barrier
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DOI：
10.1111/j.1528-1167.2012.03472.x
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发表时间：
2012-06-01
期刊：
影响因子：
5.6
通讯作者：
Janigro, Damir
中科院分区：
文献类型：
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作者：
Janigro, Damir
癫痫发作只能由癫痫神经元引发的信条最近受到了挑战。关键的星形胶质细胞-神经元通信的识别，以及星形胶质细胞和脑内皮细胞之间的密切相互作用和串扰，已经将注意力转移到血脑屏障（BBB）和神经血管单元。因此，对癫痫发作和癫痫发生机制的研究现在包括对脑血流和脑微血管通透性的研究。例如，已提出血脑屏障处的白细胞粘附分子作为匹鲁卡品诱导的癫痫持续状态的起始因子发挥作用，并且具有强血脑屏障病因的病毒感染模型已用于研究癫痫发生。最后，事实上，在非癫痫受试者的癫痫发作可以触发血脑屏障破坏，以及通过管理有效的抗癫痫血脑屏障修复药物获得的抗癫痫发作的效果，增加了对神经炎症的兴趣;循环白细胞和常驻小胶质细胞已在这种情况下进行了研究。本综述的双重范围如下：（1）概述BBB损伤和免疫细胞活化在癫痫发作疾病中的作用;（2）解释脑血管通透性增加如何导致神经元失活。癫痫发作与外周炎症和血脑屏障功能障碍的时间顺序仍有待澄清。例如，癫痫发作是否会引起全身性炎症，反之亦然，仍然存在争议。癫痫发作的基本触发因素的地形定位也仍然存在争议：癫痫发作产生所需的免疫机制是脑特异性的，还是全身免疫激活足以改变神经元的兴奋性？最后，血脑屏障渗漏的致病作用仍然是一个很大程度上尚未解决的问题。
The credo that epileptic seizures can be initiated only by epileptic neurons has been recently challenged. The recognition of key astrocytic-neuronal communication, and the close interaction and crosstalk between astrocytes and brain endothelial cells, has shifted attention to the bloodbrain barrier (BBB) and the neurovascular unit. Therefore, the pursuit of mechanisms of seizure generation and epileptogenesis now includes investigations of cerebral blood flow and permeability of cerebral microvessels. For example, leukocyte adhesion molecules at the BBB have been proposed to play a role as an initiating factor for pilocarpine-induced status epilepticus, and a viral infection model with a strong BBB etiology has been used to study epileptogenesis. Finally, the fact that in nonepileptic subjects seizures can be triggered by BBB disruption, together with the antiseizure effects obtained by administration of potent antiinflammatory BBB repair drugs, has increased the interest in neuroinflammation; both circulating leukocytes and resident microglia have been studied in this context. The dual scope of this review is the following: (1) outline the proposed role of BBB damage and immune cell activation in seizure disorders; and (2) explain how increased cerebrovascular permeability causes neuronal misfiring. The temporal sequence linking seizures to peripheral inflammation and BBB dysfunction remains to be clarified. For example, it is still debated whether seizures cause systemic inflammation or vice versa. The topographic localization of fundamental triggers of epileptic seizures also remains controversial: Are immunologic mechanisms required for seizure generation brain-specific or is systemic activation of immunity sufficient to alter neuronal excitability? Finally, the causative role of BBB leakage remains a largely unresolved issue.