PET imaging identifies anti-inflammatory effects of fluoxetine and a correlation of glucose metabolism during epileptogenesis with chronic seizure frequency

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2024-10-05 DOI:10.1016/j.neuropharm.2024.110178

Marion Bankstahl , Ina Jahreis , Bettina J. Wolf , Tobias L. Ross , Jens P. Bankstahl , Pablo Bascuñana

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Abstract

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 ¹⁸F-FDG (7 days post-SE), ¹⁸F-GE180 (15 days post-SE) and ¹⁸F-flumazenil positron emission tomography (PET, 21 days post-SE). Uptake (¹⁸F-FDG), volume of distribution (¹⁸F-GE180) and binding potential (¹⁸F-flumazenil) were calculated. In addition, hyperexcitability testing and video-EEG monitoring were performed.

Fluoxetine treatment did not alter brain glucose metabolism. ¹⁸F-GE180 PET indicated lower neuroinflammation in the hippocampus of treated animals (−22.6%, p = 0.042), but no differences were found in GABA_A 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.

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PET 成像确定了氟西汀的抗炎作用以及癫痫发生过程中葡萄糖代谢与慢性癫痫发作频率的相关性。

血清素能系统在癫痫发生过程中和慢性癫痫中发生改变，因此选择性血清素再摄取抑制剂成为抗癫痫治疗的有趣候选药物。在这项研究中，我们旨在评估氟西汀在实验性癫痫发生过程中的疾病调节作用。锂-匹罗卡品诱发癫痫状态（SE），雌性大鼠接受药物或氟西汀治疗，为期15天。动物分别接受了18F-FDG（SE后7天）、18F-GE180（SE后15天）和18F-氟马西尼正电子发射断层扫描（PET，SE后21天）。计算了摄取量（18F-FDG）、分布容积（18F-GE180）和结合电位（18F-氟马西尼）。此外，还进行了过度兴奋测试和视频脑电图监测。氟西汀治疗没有改变大脑葡萄糖代谢。18F-GE180 PET显示治疗动物海马区的神经炎症程度较低（-22.6%，P=0.042），但在GABAA受体密度方面未发现差异。视频脑电图监测并未显示治疗对癫痫发作频率的影响。然而，与治疗无关的是，SE 7 天后海马 FDG 摄取与慢性期癫痫发作频率相关（r=-0.58；p=0.015）。氟西汀治疗可在大鼠癫痫发生过程中发挥抗炎作用。然而，这种作用并没有改变疾病的结局。重要的是，癫痫发生早期的 FDG-PET 显示出生物标志物的潜力，因为葡萄糖代谢较高与慢性期癫痫发作频率较低相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).