Department of Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany; Institute of Pharmacology and Toxicology, University of Veterinary Medicine Hannover, Hannover, Germany; Department of Biological Sciences and Pathobiology, Institute of Pharmacology, University of Veterinary Medicine Vienna, Vienna, Austria.
Institute of Pharmacology and Toxicology, University of Veterinary Medicine Hannover, Hannover, Germany; Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
Neuropharmacology. 2024 Dec 15;261:110178. doi: 10.1016/j.neuropharm.2024.110178. Epub 2024 Oct 5.
The serotonergic system has shown to be altered during epileptogenesis and in chronic epilepsy, making selective serotonin reuptake inhibitors interesting candidates for antiepileptogenic therapy. In this study, we aimed to evaluate disease-modifying effects of fluoxetine during experimental epileptogenesis. Status epilepticus (SE) was induced by lithium-pilocarpine, and female rats were treated either with vehicle or fluoxetine over 15 days. Animals were subjected to F-FDG (7 days post-SE), F-GE180 (15 days post-SE) and F-flumazenil positron emission tomography (PET, 21 days post-SE). Uptake (F-FDG), volume of distribution (F-GE180) and binding potential (F-flumazenil) were calculated. In addition, hyperexcitability testing and video-EEG monitoring were performed. Fluoxetine treatment did not alter brain glucose metabolism. F-GE180 PET indicated lower neuroinflammation in the hippocampus of treated animals (-22.6%, p = 0.042), but no differences were found in GABA receptor density. Video-EEG monitoring did not reveal a treatment effect on seizure frequency. However, independently of the treatment, hippocampal FDG uptake 7 days after SE correlated with seizure frequency during the chronic phase (r = -0.58; p = 0.015). Fluoxetine treatment exerted anti-inflammatory effects in rats during epileptogenesis. However, this effect did not alter disease outcome. Importantly, FDG-PET in early epileptogenesis showed biomarker potential as higher glucose metabolism correlated to lower seizure frequency in the chronic phase.
血清素能系统在癫痫发生和慢性癫痫中显示出改变，使得选择性 5-羟色胺再摄取抑制剂成为抗癫痫发生治疗的有前途的候选药物。在这项研究中，我们旨在评估氟西汀在实验性癫痫发生中的疾病修饰作用。癫痫持续状态（SE）通过锂-匹罗卡品诱导，雌性大鼠在 15 天内用载体或氟西汀治疗。动物接受 F-FDG（SE 后 7 天）、F-GE180（SE 后 15 天）和 F-flumazenil 正电子发射断层扫描（PET，SE 后 21 天）。计算摄取（F-FDG）、分布容积（F-GE180）和结合潜能（F-flumazenil）。此外，进行了超兴奋性测试和视频-EEG 监测。氟西汀治疗并未改变大脑葡萄糖代谢。F-GE180 PET 表明治疗动物的海马体神经炎症较低（-22.6%，p=0.042），但 GABA 受体密度没有差异。视频-EEG 监测未显示治疗对发作频率的影响。然而，无论是否接受治疗，SE 后 7 天的海马 FDG 摄取与慢性期的发作频率相关（r=-0.58；p=0.015）。氟西汀治疗在癫痫发生期间对大鼠具有抗炎作用。然而，这种作用并未改变疾病结局。重要的是，早期癫痫发生中的 FDG-PET 显示出生物标志物潜力，因为较高的葡萄糖代谢与慢性期较低的发作频率相关。
