Department of Biomedical Sciences and CNR Institute of Neuroscience, University of Padova Padova, Italy.
Department of (Neuro)Pathology, Academic Medical Center, and Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, Netherlands ; SEIN - Stichting Epilepsie Instellingen Nederland Heemstede, Netherlands.
Front Cell Neurosci. 2014 Jun 6;8:155. doi: 10.3389/fncel.2014.00155. eCollection 2014.
Epilepsy is a neurological disorder characterized by a hyperexcitable brain tissue and unpredictable seizures, i.e., aberrant firing discharges in large neuronal populations. It is well established that proinflammatory cytokines, in addition to their canonical involvement in the immune response, have a crucial role in the mechanism of seizure generation. The purpose of the present study was to investigate the role of interleukin-1β (IL-1β) and high mobility group B1 (HMGB1) in the generation of seizure-like discharges using two models of focal epilepsy in a rat entorhinal cortex slice preparation. Seizure like-discharges were evoked by either slice perfusion with low Mg(2+) and picrotoxin or with a double NMDA local stimulation in the presence of the proconvulsant 4-amino-pyridine. The effects of IL-1β or HMGB1 were evaluated by monitoring seizure discharge generation through laser scanning microscope imaging of Ca(2+) signals from neurons and astrocytes. In the picrotoxin model, we revealed that both cytokines increased the mean frequency of spontaneous ictal-like discharges, whereas only IL-1β reduced the latency and prolonged the duration of the first ictal-like event. In the second model, a single NMDA pulse, per se ineffective, became successful when it was performed after IL-β or HMGB1 local applications. These findings demonstrate that both IL-1β and HMGB1 can rapidly lower focal ictal event threshold and strengthen the possibility that targeting these inflammatory pathways may represent an effective therapeutic strategy to prevent seizures.
癫痫是一种以脑组织过度兴奋和不可预测的癫痫发作为特征的神经系统疾病，即大量神经元群体的异常放电。众所周知，促炎细胞因子除了在免疫反应中的经典作用外，在癫痫发作的机制中也起着至关重要的作用。本研究的目的是使用大鼠内嗅皮层切片制备中的两种局灶性癫痫模型，研究白细胞介素-1β (IL-1β) 和高迁移率族蛋白 B1 (HMGB1) 在癫痫样放电产生中的作用。通过低镁 2+和苦毒蕈碱灌流或在促惊厥剂 4-氨基吡啶存在下对 NMDA 进行双重局部刺激，诱发癫痫样放电。通过激光扫描显微镜对神经元和星形胶质细胞的 Ca 2+信号进行成像，监测癫痫放电的产生，评估 IL-1β 或 HMGB1 的作用。在苦毒蕈碱模型中，我们发现两种细胞因子都增加了自发癫痫样放电的平均频率，而只有 IL-1β 降低了首次癫痫样事件的潜伏期并延长了其持续时间。在第二个模型中，单个 NMDA 脉冲本身无效，但在局部应用 IL-β 或 HMGB1 后，其变得有效。这些发现表明，IL-1β 和 HMGB1 都可以迅速降低局灶性癫痫事件的阈值，并且靶向这些炎症途径可能是预防癫痫发作的有效治疗策略。
