Noé Francesco M, Bellistri Elisa, Colciaghi Francesca, Cipelletti Barbara, Battaglia Giorgio, de Curtis Marco, Librizzi Laura
Unit of Clinical Epileptology and Experimental Neurophysiology, Carlo Besta Neurological Institute Foundation, Milan, Italy.
Unit of Molecular Neuroanatomy and Pathogenesis, Carlo Besta Neurological Institute Foundation, Milan, Italy.
Epilepsia. 2016 Jun;57(6):967-76. doi: 10.1111/epi.13394. Epub 2016 May 13.
Systemic administration of kainic acid (KA) is a widely used procedure utilized to develop a model of temporal lobe epilepsy (TLE). Despite its ability to induce status epilepticus (SE) in vivo, KA applied to in vitro preparations induces only interictal-like activity and/or isolated ictal discharges. The possibility that extravasation of the serum protein albumin from the vascular compartment enhances KA-induced brain excitability is investigated here.
Epileptiform activity was induced by arterial perfusion of 6 μm KA in the in vitro isolated guinea pig brain preparation. Simultaneous field potential recordings were carried out bilaterally from limbic (CA1, dentate gyrus [DG], and entorhinal cortex) and extralimbic regions (piriform cortex and neocortex). Blood-brain barrier (BBB) breakdown associated with KA-induced epileptiform activity was assessed by parenchymal leakage of intravascular fluorescein-isothiocyanate albumin. Seizure-induced brain inflammation was evaluated by western blot analysis of interleukin (IL)-1β expression in brain tissue.
KA infusion caused synchronized activity at 15-30 Hz in limbic (but not extralimbic) cortical areas, associated with a brief, single seizure-like event. A second bolus of KA, 60 min after the induction of the first ictal event, did not further enhance excitability. Perfusion of serum albumin between the two administrations of KA enhanced epileptiform discharges and allowed a recurrent ictal event during the second KA infusion.
Our data show that arterial KA administration selectively alters the synchronization of limbic networks. However, KA is not sufficient to generate recurrent seizures unless serum albumin is co-perfused during KA administration. These findings suggest a role of serum albumin in facilitating acute seizure generation.
全身给予海藻酸（KA）是一种广泛用于建立颞叶癫痫（TLE）模型的方法。尽管其能够在体内诱发癫痫持续状态（SE），但应用于体外制剂时，KA仅诱导发作间期样活动和/或孤立的发作期放电。本文研究了血清蛋白白蛋白从血管腔外渗增强KA诱导的脑兴奋性的可能性。
在体外分离的豚鼠脑制剂中，通过动脉灌注6μm KA诱导癫痫样活动。从边缘（CA1、齿状回[DG]和内嗅皮质）和边缘外区域（梨状皮质和新皮质）双侧同时进行场电位记录。通过血管内异硫氰酸荧光素白蛋白的实质渗漏评估与KA诱导的癫痫样活动相关的血脑屏障（BBB）破坏。通过对脑组织中白细胞介素（IL）-1β表达的蛋白质印迹分析评估癫痫发作诱导的脑炎症。
KA灌注在边缘（而非边缘外）皮质区域引起15 - 30Hz的同步活动，与短暂的单次癫痫样事件相关。在首次发作事件诱导后60分钟给予第二次KA推注，并未进一步增强兴奋性。在两次KA给药之间灌注血清白蛋白增强了癫痫样放电，并在第二次KA灌注期间允许复发性发作事件。
我们的数据表明，动脉给予KA选择性地改变边缘网络的同步性。然而，除非在给予KA期间同时灌注血清白蛋白，否则KA不足以产生复发性癫痫发作。这些发现表明血清白蛋白在促进急性癫痫发作产生中起作用。
