Brain inflammation in a chronic epilepsy model: Evolving pattern of the translocator protein during epileptogenesis
Brain inflammation in a chronic epilepsy model: Evolving pattern of the translocator protein during epileptogenesis
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DOI：
10.1016/j.nbd.2015.09.004
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发表时间：
2015-10-01
影响因子：
6.1
通讯作者：
Dedeurwaerdere, Stefanie
中科院分区：
文献类型：
--
作者：
Amhaoul, Halima;Hamaide, Julie;Dedeurwaerdere, Stefanie
目的：颞叶癫痫神经病理学的一个标志是脑炎症，它被认为是治疗的生物标志物和新的机制靶点。转运蛋白（TSPO），由于其在神经炎症条件下的高上调和选择性PET示踪剂的可用性，是一个候选目标。利用这一目标的一个重要步骤是彻底表征癫痫发生过程中TSPO的时空分布。在癫痫发生过程中的五个时间点评价了几个脑区域中的TSPO表达、小胶质细胞活化、星形胶质细胞反应性和细胞损失，包括海人酸诱导的癫痫持续状态（KASE）模型（n = 52）和对照Wistar Han大鼠（n = 33）的慢性癫痫阶段。还确定了慢性期的癫痫发作负担。此外，F-18-PBR111 PET/MRI扫描纵向收购在另外四个KASE animals.Results：TSPO表达测量与体外和体内技术在每个时间点显着增加，达到高峰后两周SE边缘系统。可以证明TSPO表达与活化的小胶质细胞（p <0.001; r = 0.7）以及细胞损失（p <0.001; r = 0.8）之间的显著关联。自发性癫痫发作和TSPO上调在几个脑区与增加TSPO expression.Conclusions：TSPO表达动态上调癫痫发生过程中，持续在慢性期，并与小胶质细胞活化，而不是反应性星形胶质细胞之间存在显着的正相关性。TSPO表达与自发性癫痫发作相关，其在潜伏期的高表达可能提示其是疾病个体发生的重要转换点，可通过PET成像进一步研究。(C)2015 Elsevier Inc. All rights reserved.
Aims: A hallmark in the neuropathology of temporal lobe epilepsy is brain inflammation which has been suggested as both a biomarker and a new mechanistic target for treatments. The translocator protein (TSPO), due to its high upregulation under neuroinflammatory conditions and the availability of selective PET tracers, is a candidate target. An important step to exploit this target is a thorough characterisation of the spatiotemporal profile of TSPO during epileptogenesis.Methods: TSPO expression, microglial activation, astrocyte reactivity and cell loss in several brain regions were evaluated at five time points during epileptogenesis, including the chronic epilepsy phase in the kainic acid-induced status epilepticus (KASE) model (n = 52) and control Wistar Han rats (n = 33). Seizure burden was also determined in the chronic phase. Furthermore, F-18-PBR111 PET/MRI scans were acquired longitudinally in an additional four KASE animals.Results: TSPO expression measured with in vitro and in vivo techniques was significantly increased at each time point and peaked two weeks post-SE in the limbic system. A prominent association between TSPO expression and activated microglia (p < 0.001; r = 0.7), as well as cell loss (p < 0.001; r = 0.8) could be demonstrated. There was a significant positive correlation between spontaneous seizures and TSPO upregulation in several brain regions with increased TSPO expression.Conclusions: TSPO expression was dynamically upregulated during epileptogenesis, persisted in the chronic phase and correlated with microglia activation rather than reactive astrocytes. TSPO expression was correlating with spontaneous seizures and its high expression during the latent phase might possibly suggest being an important switching point in disease ontogenesis which could be further investigated by PET imaging. (C) 2015 Elsevier Inc. All rights reserved.