Savotchenko Alina, Klymenko Mariia, Shypshyna Mariia, Isaev Dmytro
Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kyiv, Ukraine.
Laboratory of Synaptic Transmission, Bogomoletz Institute of Physiology, Kyiv, Ukraine.
Front Cell Neurosci. 2023 Mar 9;17:1101006. doi: 10.3389/fncel.2023.1101006. eCollection 2023.
A variety of clinical observations and studies in animal models of temporal lobe epilepsy (TLE) reveal dysfunction of blood-brain barrier (BBB) during seizures. It is accompanied by shifts in ionic composition, imbalance in transmitters and metabolic products, extravasation of blood plasma proteins in the interstitial fluid, causing further abnormal neuronal activity. A significant amount of blood components capable of causing seizures get through the BBB due to its disruption. And only thrombin has been demonstrated to generate early-onset seizures. Using the whole-cell recordings from the single hippocampal neurons we recently showed the induction of epileptiform firing activity immediately after the addition of thrombin to the blood plasma ionic media. In the present work, we mimic some effects of BBB disruption to examine the effect of modified blood plasma artificial cerebrospinal fluid (ACSF) on the excitability of hippocampal neurons and the role of serum protein thrombin in seizure susceptibility. Comparative analysis of model conditions simulating BBB dysfunction was performed using the lithium-pilocarpine model of TLE, which most clearly reflects the BBB disruption in the acute stage. Our results demonstrate the particular role of thrombin in seizure-onset in conditions of BBB disruption.
在颞叶癫痫（TLE）动物模型中的各种临床观察和研究表明，癫痫发作期间血脑屏障（BBB）功能失调。这伴随着离子成分的变化、递质和代谢产物的失衡、血浆蛋白在间质液中的渗出，进而导致神经元活动进一步异常。由于血脑屏障的破坏，大量能够引发癫痫发作的血液成分得以通过。并且只有凝血酶被证明会引发早发性癫痫发作。我们最近通过对单个海马神经元进行全细胞记录发现，向血浆离子介质中添加凝血酶后立即诱导出癫痫样放电活动。在本研究中，我们模拟血脑屏障破坏的一些效应，以研究改良的血浆人工脑脊液（ACSF）对海马神经元兴奋性的影响以及血清蛋白凝血酶在癫痫易感性中的作用。使用最能清晰反映急性期血脑屏障破坏的TLE锂 - 匹罗卡品模型，对模拟血脑屏障功能障碍的模型条件进行了比较分析。我们的结果证明了凝血酶在血脑屏障破坏情况下癫痫发作起始中的特殊作用。
