Epileptogenesis-associated brain inflammation might be a promising target to prevent or attenuate epileptogenesis. Positron emission tomography (PET) imaging targeting the translocator protein (TSPO) was applied here to quantify effects of different dosing regimens of the anti-inflammatory drug minocycline during the latent phase in two rodent models of epileptogenesis. After induction of epileptogenesis by status epilepticus (SE), rats were treated with minocycline for 7 days (25 or 50 mg/kg) and mice for 5 or 10 days (50 or 100 mg/kg). All animals were subjected to scans at 1 and 2 weeks post-SE. Radiotracer distribution was analyzed and statistical parametric mapping (SPM) was performed, as well as histological analysis of astroglial activation and neuronal cell loss. Atlas-based analysis of [18F]GE180 PET in rats revealed a dose-dependent regional decrease of TSPO expression at 2 weeks post-SE. Results of SPM analysis depicted a treatment effect already at 1 week post-SE in rats treated with the higher minocycline dose. In mice, TSPO PET imaging did not reveal any treatment effects whereas histology identified only a treatment-related reduction in dispersion of dentate gyrus neurons. TSPO PET served as an auspicious tool for temporal monitoring and quantification of anti-inflammatory effects during epileptogenesis. Importantly, the findings underline the need to applying more than one animal model to avoid missing treatment effects. For future studies, the setup is ready to be applied in combination with seizure monitoring to investigate the relationship between individual early treatment response and disease outcome.

中文翻译：

---

TSPO PET 确定了两种啮齿动物癫痫发生模型中不同的抗炎米诺环素治疗反应。

癫痫发生相关的脑部炎症可能是预防或减轻癫痫发生的有希望的目标。在此应用针对易位蛋白（TSPO）的正电子发射断层扫描（PET）成像来量化抗炎药物米诺环素在两种啮齿动物癫痫发生模型的潜伏期期间不同给药方案的效果。通过癫痫持续状态 (SE) 诱导癫痫发生后，用米诺环素治疗大鼠 7 天（25 或 50 mg/kg），用米诺环素治疗小鼠 5 或 10 天（50 或 100 mg/kg）。所有动物均在 SE 后 1 周和 2 周接受扫描。分析了放射性示踪剂的分布并进行了统计参数绘图（SPM），以及星形胶质细胞活化和神经元细胞损失的组织学分析。基于图谱的大鼠 [18F]GE180 PET 分析显示，SE 后 2 周，TSPO 表达出现剂量依赖性区域下降。SPM 分析结果显示了 SE 后 1 周时用较高米诺环素剂量治疗的大鼠的治疗效果。在小鼠中，TSPO PET 成像没有显示任何治疗效果，而组织学仅发现齿状回神经元分散性与治疗相关的减少。TSPO PET 是癫痫发生过程中抗炎作用的时间监测和量化的有利工具。重要的是，研究结果强调需要应用不止一种动物模型以避免错过治疗效果。对于未来的研究，该设置已准备好与癫痫监测结合应用，以研究个体早期治疗反应与疾病结果之间的关系。