血脑屏障破坏后白蛋白进入中枢导致脑兴奋性增高的机制

The Mechanism of Eliciting Brain Excitability Which Caused by Albumin Entered into Centra after Blood-brain Barrier Dysfunction

癫反复发作的机制一直未完全明了,当前的研究表明癫的反复发作,导致血脑屏障破坏,随后外周血中白蛋白进入中枢,但其在脑脊液中的浓度难以检测。进入中枢的白蛋白通过依赖转化生长因子-β(TGF-β)信号通路导致钾内向整流通道和水通道蛋白4下调,诱导和维持中枢的神经炎症,影响缝隙连接偶联,参与兴奋性递质转运;以及通过非依赖TGF-β信号通路上调基质金属蛋白酶-9,降低扩散性去极化,导致神经元死亡,缓冲抗癫药物浓度等影响脑的兴奋性,促进癫的反复发作。而针对相关机制的干预研究也提供了抗新思路。

The mechanism of epilepsy recurrence is constantly unclear, the current research indicated that the recurrence of epilepsy caused the disruption of blood-brain barrier, which further caused albumin in periphery blood to enter into centra, but albumin is detected difficultly. When albumin entered into centra, it upregulated Kir 4.1 and AQP4 expression, induced and maintained central neuroinflammation, lowered ligandin in gap junction coupling and promoted excitatory transmitter transportation through dependent TGF-β pathway. And it also upregulated MMP-9 expression, lowered spreading depolarizations threshold, promoted the death of neuron and buffed the AEDs concentration through independent TGF-β pathway, all of which elicited the brain excitability and the recurrence of epilepsy. The intervention for relevant mechanism also suggested a new antiepileptic orientation.