PK ('peripheral benzodiazepine') - Binding sites in the CNS indicate early and discrete brain lesions: Microautoradiographic detection of [H-3]PK11195 binding to activated microglia
PK ('peripheral benzodiazepine') - Binding sites in the CNS indicate early and discrete brain lesions: Microautoradiographic detection of [H-3]PK11195 binding to activated microglia
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DOI：
10.1023/a:1018567510105
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发表时间：
1997-02-01
期刊：
影响因子：
--
通讯作者：
Kreutzberg, GW
中科院分区：
文献类型：
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作者：
Banati, RB;Myers, R;Kreutzberg, GW
异喹啉PK 11195被认为是受损脑中神经胶质病理学的标志物。本研究的目的是阐明其结合位点在中枢神经系统中的精确细胞定位。在这里，我们报告说，在面神经轴突切断术后的面神经核-一个病变引起逆行神经元反应，而没有神经细胞死亡，同时保持血脑屏障完整-激活的小胶质细胞是病变诱导的PK 11195结合增加的主要来源。同样，增加PK 11195结合后，观察到在薄核顺行神经元损伤后坐骨神经横断。使用单一异构体R-PK 11195，在外周神经损伤后4天观察到PK 11195结合的峰值，与众所周知的小胶质细胞活化的时间过程一致。照相乳剂显微放射自显影证实了PK 11195与活化的小胶质细胞结合的限制。PK 11195结合面神经核后看到的选择性细胞死亡的毒性蓖麻毒素，一种病变，是伴随着小胶质细胞迅速转化为吞噬细胞的逆行自杀运输，是不高于轴突切断术后看到的。这表明，小胶质细胞完全转化为实质吞噬细胞是没有必要达到最大水平的PK 11195结合。因此，PK 11195是一种非常适合检测细微脑病理学区域中小胶质细胞活化的标记物，其中血脑屏障功能的紊乱或巨噬细胞和炎性细胞的存在都不表明正在进行的疾病过程。
The isoquinoline PK11195 has been suggested as a marker of glial pathology in the lesioned brain. The aim of the present study is to clarify the precise cellular location of its binding site in the central nervous system. Here, we report that in the facial nucleus after facial nerve axotomy- a lesion causing a retrograde neuronal reaction without nerve cell death while keeping the blood-brain barrier intact - activated microglia are the predominant source of lesion-induced increases of PK11195 binding. Likewise, increased PK11195 binding is seen in the gracile nucleus after anterograde neuronal injury following sciatic nerve transection. The peak of PK11195 binding, using the single isomer R-PK11195, was observed 4 days after the peripheral nerve lesion, consistent with the well-known time course of microglial activation. Photoemulsion microautoradiography confirmed the restriction of PK11195 binding to activated microglia. The increase of PK11195 binding in the facial nucleus seen after selective cell death of facial motoneurons by retrograde suicide transport of toxic ricin, a lesion that is accompanied by the rapid transformation of microglia into phagocytes, was no higher than that seen following axotomy. This suggests that the full transformation of microglia into parenchymal phagocytes is not necessary to reach maximal levels of PK11195 binding. PK11195, therefore, is a well-suited marker to detect microglial activation in areas of subtle brain pathology, where neither a disturbance of the blood-brain barrier function nor the presence of macrophages and inflammatory cells indicate an on-going disease process.