Departments of Molecular Medicine Cell Biology, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, U.S.A.
Epilepsia. 2012 Nov;53(11):1877-86. doi: 10.1111/j.1528-1167.2012.03637.x. Epub 2012 Aug 20.
The blood-brain barrier (BBB) is located within a unique anatomic interface and has functional ramifications to most of the brain and blood cells. In the past, the BBB was considered a pharmacokinetic impediment to antiepileptic drug penetration into the brain; nowadays it is becoming increasingly evident that targeting of the damaged or dysfunctional BBB may represent a therapeutic approach to reduce seizure burden. Several studies have investigated the mechanisms linking the onset and sustainment of seizures to BBB dysfunction. These studies have shown that the BBB is at the crossroad of a multifactorial pathophysiologic process that involves changes in brain milieu, altered neuroglial physiology, development of brain inflammation, leukocyte-endothelial interactions, faulty angiogenesis, and hemodynamic changes leading to energy mismatch. A number of knowledge gaps, conflicting points of view, and discordance between clinical and experimental data currently characterize this field of neuroscience. As more pieces are added to this puzzle, it is apparent that each mechanism needs to be validated in an appropriate clinical context. We now offer a BBB-centric view of seizure disorders, linking several aspects of seizures and epilepsy physiopathology to BBB dysfunction. We have reviewed the therapeutic, antiseizure effect of drugs that promote BBB repair. We also present BBB neuroimaging as a tool to correlate BBB restoration to seizure mitigation. Add-on cerebrovascular drug could be of efficacy in reducing seizure burden when used in association with neuronal antiepileptic drugs.
血脑屏障(BBB)位于独特的解剖界面内,对大脑和大多数血细胞的功能都有影响。过去,BBB 被认为是抗癫痫药物进入大脑的药代动力学障碍;如今,越来越明显的是,靶向受损或功能失调的 BBB 可能代表一种减少癫痫发作负担的治疗方法。有几项研究调查了将癫痫发作的发作和持续与 BBB 功能障碍联系起来的机制。这些研究表明,BBB 处于涉及大脑环境变化、神经胶质生理学改变、脑炎症发展、白细胞-内皮细胞相互作用、错误的血管生成以及导致能量不匹配的血液动力学变化的多因素病理生理过程的交叉点。目前,该神经科学领域存在许多知识空白、观点冲突以及临床与实验数据之间的不和谐。随着拼图的不断增加,很明显,每个机制都需要在适当的临床环境中进行验证。我们现在提供了一种以 BBB 为中心的癫痫发作疾病观点,将癫痫发作和癫痫病理生理学的几个方面与 BBB 功能障碍联系起来。我们回顾了促进 BBB 修复的药物的治疗、抗癫痫作用。我们还提出了 BBB 神经影像学作为一种将 BBB 恢复与癫痫缓解相关联的工具。当与神经元抗癫痫药物联合使用时,附加脑血管药物在降低癫痫发作负担方面可能有效。