Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
Parkinsonism Relat Disord. 2009 Dec;15 Suppl 3:S200-4. doi: 10.1016/S1353-8020(09)70814-4.
Evidence shows that neuronal injury accompanies neuroinflammatory reactions in the brain, and well as in Parkinson's disease (PD) animal models, in which the loss of dopamine neurons is associated with the activation of microglia in the substantia nigra. Activated microglia can be illustrated in vivo using Positron emission tomography and (11)C-PK11195. However, this tracer cannot distinguish between the two aspects of microglial function (protective and inflammatory). To solve this problem, we can use a dopamine transporter marker, [(11)C]CFT, which binds to the dopamine transporter. The binding of the tracer reflects the viability of the presynaptic dopaminergic neurons, as reported in a multicenter trial using single photon emission tomography (SPECT) with [(123I)]beta-CIT, a SPECT version of [(11)C]CFT. In early drug-naïve PD patients, these two tracers showed a unique pattern of binding, (11)C-PK11195 binding potential in the midbrain was correlated inversely with [(11)C]CFT binding in the putamen, and midbrain (11)C-PK11195 binding was found to be positively correlated with the motor severity of parkinsonism. These results indicate that early introduction of a neuroprotective drug to suppress microglial activation is favorable in PD and that (11)C-PK11195 can be used to monitor the progression of the disease. As the disease progressed, the [(11)C]CFT binding was further decreased, and the microglial activation spread over the entire brain. This paper briefly summarizes the neuroinflammation induced by microglia in PD and describes an in vivo aspect of the neuroinflammation in the PD brain by focusing on the covarying changes in microglial activation and neuronal damage.
证据表明，神经元损伤伴随着大脑中的神经炎症反应，以及帕金森病（PD）动物模型中的神经炎症反应，其中多巴胺神经元的丧失与黑质中小胶质细胞的激活有关。使用正电子发射断层扫描和 (11)C-PK11195 可以在体内显示激活的小胶质细胞。然而，这种示踪剂不能区分小胶质细胞功能的两个方面（保护和炎症）。为了解决这个问题，我们可以使用多巴胺转运体标记物 [(11)C]CFT，它与多巴胺转运体结合。示踪剂的结合反映了突触前多巴胺能神经元的活力，这在使用单光子发射断层扫描（SPECT）和 [(123I)]beta-CIT 的多中心试验中得到了报道，[(11)C]CFT 的 SPECT 版本。在早期未经药物治疗的 PD 患者中，这两种示踪剂显示出一种独特的结合模式，中脑 (11)C-PK11195 结合潜力与壳核中的 [(11)C]CFT 结合呈负相关，并且中脑 (11)C-PK11195 结合与帕金森病运动严重程度呈正相关。这些结果表明，早期引入神经保护药物抑制小胶质细胞激活对 PD 有利，并且 (11)C-PK11195 可用于监测疾病的进展。随着疾病的进展，[(11)C]CFT 结合进一步降低，小胶质细胞激活扩散到整个大脑。本文简要总结了 PD 中小胶质细胞引起的神经炎症，并通过重点关注小胶质细胞激活和神经元损伤的变化，描述了 PD 大脑中神经炎症的一个体内方面。
