Skopin Mark D, Bayat Arezou, Kurada Lalitha, Siddu Mithilesh, Joshi Sweta, Zelano Christina M, Koubeissi Mohamad Z
Department of Neurology, George Washington University, Washington, DC, 20037, USA.
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Seizure. 2020 Oct;81:1-7. doi: 10.1016/j.seizure.2020.07.008. Epub 2020 Jul 10.
Tissue remodeling has been described in brain circuits that are involved in the generation and propagation of epileptic seizures. Human and animal studies suggest that the anterior piriform cortex (aPC) is crucial for seizure expression in focal epilepsies. Here, we investigate the effect of kainic-acid (KA)-induced seizures on the effective connectivity of the aPC with bilateral hippocampal CA3 regions using cerebro-cerebral evoked potentials (CCEPs).
Adult male Sprague-Dawley rats were implanted with a tripolar electrode in the left aPC for stimulation and recording, and with unipolar recording electrodes in bilateral CA3 regions. Single pulse stimulations were given to the aPC and CCEPs were averaged before KA injections and after the emergence of spontaneous recurrent seizures (SRS). Similar recordings at equivalent time intervals were obtained from animals that received saline injections instead of KA (controls).
In the experimental group, the percentage change of increased amplitude of the contralateral (but not ipsilateral) CA3 CCEPs between pre-KA injection and after the emergence of SRS was significantly greater than in controls. No significant single-pulse-induced spectral change responses were observed in either epileptic or control rats when comparing pre- and post-stimulus time intervals. Also, we found no correlation between seizure frequency and the extent of amplitude changes in the CCEPs.
In the KA model, epileptogenesis results in plastic changes that manifest as an amplification of evoked potential amplitudes recorded in the contralateral hippocampus in response to single-pulse stimulation of the aPC. These results suggest epileptogenesis-induced facilitation of interhemispheric connectivity between the aPC and the hippocampus. Since the amplitude increase of the contralateral CCEP is a possible in vivo biomarker of epilepsy, any intervention (e.g. neuromodulatory) that can reverse this phenomenon may hold a potential antiepileptic efficacy.
在参与癫痫发作产生和传播的脑回路中已观察到组织重塑现象。人体和动物研究表明，前梨状皮质（aPC）对于局灶性癫痫发作的表现至关重要。在此，我们使用脑-脑诱发电位（CCEPs）研究了海藻酸（KA）诱导的癫痫发作对aPC与双侧海马CA3区之间有效连接性的影响。
成年雄性Sprague-Dawley大鼠在左侧aPC植入三极电极用于刺激和记录，并在双侧CA3区植入单极记录电极。在注射KA之前以及出现自发性反复癫痫发作（SRS）之后，对aPC进行单脉冲刺激并对CCEPs进行平均。从接受盐水注射而非KA注射的动物（对照组）中，在相同时间间隔获得类似记录。
在实验组中，KA注射前与SRS出现后，对侧（而非同侧）CA3区CCEPs振幅增加的百分比变化显著大于对照组。在比较刺激前和刺激后的时间间隔时，癫痫大鼠和对照大鼠均未观察到明显的单脉冲诱发频谱变化反应。此外，我们发现癫痫发作频率与CCEPs振幅变化程度之间无相关性。
在KA模型中，癫痫发生导致可塑性变化，表现为对aPC进行单脉冲刺激时，对侧海马记录到的诱发电位振幅放大。这些结果表明癫痫发生诱导了aPC与海马之间半球间连接性的增强。由于对侧CCEP振幅增加可能是癫痫的一种体内生物标志物，任何能够逆转这种现象的干预措施（例如神经调节）可能具有潜在的抗癫痫疗效。
