Blood-brain barrier, bulk flow, and interstitial clearance in epilepsy.
Blood-brain barrier, bulk flow, and interstitial clearance in epilepsy.
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DOI：
10.1016/j.jneumeth.2015.06.011
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发表时间：
2016-02-15
影响因子：
3
通讯作者：
Janigro D
中科院分区：
文献类型：
--
作者：
Marchi N;Banjara M;Janigro D
了解癫痫的病理生理学意味着阐明癫痫发作之前或发作时发生的神经血管改变。脑血管功能障碍会引发或维持癫痫发作，而选择性血脑屏障（BBB）通透性的丧失是癫痫阈值的调节剂。然而，癫痫的脑血管病理超出了血脑屏障“渗漏”范围，涵盖了血管和实质事件。每当在脑血管周围观察到蛋白质异常积累时，就会调用血脑屏障破坏（BBBD）。最近的临床和实验室研究结果对 BBBD 在血清衍生产物的血管周围积聚中的独特作用提出了挑战。间质液循环（ISF）及其整体流动已成为在中枢神经系统废物清除中发挥作用的候选机制。尽管存在争议，但 ISF 流量的变化可能通过不完全的实质清除和伴随的有毒副产物积累的机制导致中枢神经系统疾病。我们总结了支持和反对 ISF 整体流动的证据，并提出了一种情况，即癫痫脑中异常的 ISF 会导致脑蛋白积累，维持病理生理学并改变抗癫痫药物的药理学。我们还描述了常规用于剖析 BBB 依赖性、血管或细胞旁机制对神经元兴奋性改变的贡献的方法。
Understanding the pathophysiology of epilepsy implies elucidating the neurovascular modifications occurring before or at time of seizures. Cerebrovascular dysfunction provokes or sustains seizures and loss of selective blood–brain barrier (BBB) permeability is a modulator of seizure threshold. However, cerebrovascular pathology in epilepsy extends beyond BBB “leakage” to encompass vascular and parenchymal events. Whenever abnormal accumulation of protein is observed surrounding brain blood vessels, BBB disruption (BBBD) was invoked. Recent clinical and laboratory findings challenged an exclusive role of BBBD in perivascular accumulation of serum-derived products. The circulation of interstitial fluid (ISF) and its bulk flow have emerged as candidate mechanisms which play a role in clearance of CNS waste. Although controversy exists, changes of ISF flow may contribute to CNS disorders through a mechanism encompassing incomplete parenchymal clearance and accompanying accumulation of toxic byproducts. We summarize the evidence in favor and against ISF bulk flow and propose a scenario where abnormal ISF in the epileptic brain allows accumulation of brain protein, sustaining pathophysiology and altering the pharmacology of antiepileptic drugs. We also describe the methods routinely used to dissect out the contribution of BBB-dependent, vascular or paracellular mechanisms to altered neuronal excitability.