Molecular imaging of microglial activation in amyotrophic lateral sclerosis.
Molecular imaging of microglial activation in amyotrophic lateral sclerosis.
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DOI：
10.1371/journal.pone.0052941
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ribeiro MJ
中科院分区：
文献类型：
--
作者：
Corcia P;Tauber C;Vercoullie J;Arlicot N;Prunier C;Praline J;Nicolas G;Venel Y;Hommet C;Baulieu JL;Cottier JP;Roussel C;Kassiou M;Guilloteau D;Ribeiro MJ
越来越多的证据表明肌萎缩侧索硬化症（ALS）患者大脑皮层中存在激活的小胶质细胞和炎症过程。活化的小胶质细胞的特征在于脑中18 kDa转运蛋白（TSPO）的表达增加，并且可能是炎症的有用生物标志物。在这项研究中，我们使用TSPO的放射性配体18F-DPA-714评估了ALS患者的神经炎症。前瞻性招募了10名可能或明确的ALS患者（均为右利手，无痴呆，未接受利鲁唑或其他可能使TSPO结合偏倚的药物治疗），8名年龄匹配的健康对照者接受了PET研究。使用Mann-Whitney检验比较两组之间的分布容积比。在ALS样本中，与小胶质细胞激活相对应的体积比值分布在初级运动皮质、辅助运动皮质和颞叶皮质中显着增加（分别为p= 0.009、p = 0.001和p =0.004）。 这些结果表明，皮质摄取的18F-DPA-714在ALS患者在疾病的“诊断时间”阶段增加。这一发现可能会提高我们对ALS病理生理学的理解，并可能成为小胶质细胞活化治疗疗效的替代标志物。
There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, 18F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney’s test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of 18F-DPA-714 was increased in ALS patients during the “time of diagnosis” phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation.