11C-PK11195 PET for the In Vivo Evaluation of Neuroinflammation in the Rat Brain After Cortical Spreading Depression
11C-PK11195 PET for the In Vivo Evaluation of Neuroinflammation in the Rat Brain After Cortical Spreading Depression
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DOI：
10.2967/jnumed.109.066498
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发表时间：
2009-11-01
影响因子：
9.3
通讯作者：
Watanabe, Yasuyoshi
中科院分区：
文献类型：
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作者：
Cui, Yilong;Takashima, Tadayuki;Watanabe, Yasuyoshi
由血浆蛋白外渗引发的神经源性炎症已被假设为与偏头痛相关的痛觉产生的关键因素。对这种炎症反应的主要免疫细胞是中枢神经系统的实质小胶质细胞。研究方法：利用外周型苯二氮卓受体的PET配体C-11-（R）-[1-（2-氯苯基）-N-甲基-N-（1-甲基丙基）3-异喹啉甲酰胺]（C-11-PK 11195）的PET技术，我们评价了在产生单侧皮质扩散性抑制后大鼠脑中小胶质细胞的激活，该刺激用于产生偏头痛实验动物模型。结果如下：我们发现，在扩散性抑郁症大鼠的同侧半球中，C-11-PK 11195的脑摄取显著增加，这完全可以被过量的未标记配体所取代。此外，C-11-PK 11195在扩散性抑郁大鼠中的结合电位显著高于假手术对照大鼠。结论：这些结果表明，作为一种炎症反应，小胶质细胞被激活的伤害性刺激诱导的皮层扩散性抑制在大鼠脑内。因此，C-11-PK 11195 PET技术可能具有诊断和治疗监测与神经炎症相关的神经系统疾病（如偏头痛）的潜力。
Neurogenic inflammation triggered by extravasation of plasma protein has been hypothesized as a key factor in the generation of the pain sensation associated with migraine. The principal immune cell that responds to this inflammation is the parenchymal microglia of the central nervous system. Methods: Using a PET technique with C-11-(R)-[1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)3-isoquinolinecarboxamide] (C-11-PK11195), a PET ligand for peripheral type-benzodiazepine receptor, we evaluated the microglial activation in the rat brain after generation of unilateral cortical spreading depression, a stimulation used to bring up an experimental animal model of migraine. Results: We found a significant increase in the brain uptake of C-11-PK11195, which was completely displaceable by the excess amounts of unlabeled ligands, in the ipsilateral hemisphere of the spreading depression generated rats. Moreover, the binding potential of C-11-PK11195 in the spreading depression-generated rats was significantly higher than that in the sham-operated control rats. Conclusion: These results suggest that as an inflammatory reaction, microglial cells are activated in response to the nociceptive stimuli induced by cortical spreading depression in the rat brain. Therefore, the C-11-PK11195 PET technique could have a potential for diagnostic and therapeutic monitoring of neurologic disorders related to neuroinflammation such as migraine.