Çarçak Nihan, Dileköz Ergin, Gülhan Rezzan, Onur Rüştü, Onat Filiz Yılmaz, Sara Yıldırım
Istanbul University, Faculty of Pharmacy, Department of Pharmacology, Istanbul, Turkey.
Gazi University, Faculty of Medicine, Department of Pharmacology, Ankara, Turkey.
Epilepsy Res. 2016 Oct;126:70-7. doi: 10.1016/j.eplepsyres.2016.06.013. Epub 2016 Jun 27.
Genetic absence epilepsy rats from Strasbourg (GAERS), a well-validated genetic rat model for typical absence epilepsy, are known to manifest a resistance to secondary generalization of abnormal focal electrical activity evoked by kindling. The mechanism of this resistance is still unclear. In order to understand the possible mechanism of kindling resistance, we investigated for the first time, the differences of short-term synaptic plasticity by using a paired-pulse paradigm as an indicator of GABAergic activity in CA1 region of hippocampus in GAERS and non-epileptic Wistar rats in-vivo.
Rats were subjected to kindling process, basolateral amygdala was stimulated twice a day, with a supra-threshold current, until they displayed limbic or convulsive seizures. One hour after the last kindling stimulation, evoked field potentials from CA1 pyramidal layer of hippocampus were recorded in-vivo under urethane anesthesia.
In response to supra-threshold kindling stimulations GAERS showed a significantly delayed kindling progression and displayed a significant increase in hippocampal excitability at early stages of kindling that is the critical for the development of convulsive seizures. In control rats that were not received kindling stimulation, paired-pulse depression (PPD) was significantly pronounced in GAERS with respect to the Wistar group. During the kindling course, PPD was gradually reduced in the Wistar rats as kindling progression was advanced. However in GAERS, PPD ratios were not significantly changed at early stages of kindling. When GAERS reached convulsive stage, their PPD ratios became similar to that of Wistar rats.
The increased inhibition in paired-pulse responses at early stages of kindling in GAERS suggests the role of augmented GABAergic activity as one of the underlying mechanisms of kindling resistance observed in genetic rat models of absence epilepsy.
来自斯特拉斯堡的遗传性失神癫痫大鼠（GAERS）是一种经过充分验证的典型失神癫痫遗传大鼠模型，已知其对点燃诱发的异常局灶性电活动的继发性泛化具有抗性。这种抗性的机制尚不清楚。为了了解点燃抗性的可能机制，我们首次以配对脉冲范式作为体内GAERS和非癫痫性Wistar大鼠海马CA1区GABA能活动指标，研究了短期突触可塑性的差异。
对大鼠进行点燃过程，每天两次以阈上电流刺激基底外侧杏仁核，直至它们出现边缘性或惊厥性癫痫发作。在最后一次点燃刺激后1小时，在乌拉坦麻醉下体内记录海马CA1锥体层的诱发场电位。
对阈上点燃刺激，GAERS的点燃进程明显延迟，且在点燃早期海马兴奋性显著增加，这对惊厥性癫痫发作的发展至关重要。在未接受点燃刺激的对照大鼠中，相对于Wistar组，GAERS的配对脉冲抑制（PPD）明显更显著。在点燃过程中，随着点燃进程的推进，Wistar大鼠的PPD逐渐降低。然而，在GAERS中，点燃早期PPD比率没有显著变化。当GAERS达到惊厥阶段时，其PPD比率变得与Wistar大鼠相似。
GAERS点燃早期配对脉冲反应中抑制作用的增强表明，增强的GABA能活动作为失神癫痫遗传大鼠模型中观察到的点燃抗性的潜在机制之一发挥了作用。
