Phase-dependent roles of reactive microglia and astrocytes in nervous system injury as delineated by imaging of peripheral benzodiazepine receptor
Phase-dependent roles of reactive microglia and astrocytes in nervous system injury as delineated by imaging of peripheral benzodiazepine receptor
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DOI：
10.1016/j.brainres.2007.04.054
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发表时间：
2007-07-09
期刊：
影响因子：
2.9
通讯作者：
Suhara, Tetsuya
中科院分区：
文献类型：
--
作者：
Maeda, Jun;Higuchi, Makoto;Suhara, Tetsuya
神经胶质细胞中外周苯二氮卓受体（PBR）水平升高已被证明在不同的神经系统损伤，而显示PBR上调的细胞的身份和时空特征仍然难以捉摸。我们研究了星形胶质细胞和小胶质细胞表达的PBR在大鼠大脑中的乙醇诱导的神经元损伤的持续时间，以澄清的意义PBR作为一种生物标志物，能够检测这些胶质细胞的一个独特的亚群参与损伤和保护神经元。PBR的水平，通过放射自显影分析确定使用特定的放射性配体，[C-11] DAA 1106，在纹状体内注射乙醇后3天开始显着增加，并在7天达到峰值。这与双重免疫荧光染色和高分辨率乳剂放射自显影的结果一致，该结果显示在损伤部位的非重叠隔室中增殖的小胶质细胞和星形胶质细胞中PBR均上调。值得注意的是，在星形胶质细胞中瞬时观察到PBR表达增加，其方式与这些细胞向炎性病变的向心迁移平行，这可能是保护完整组织不可或缺的反应。此后，星形胶质细胞PBR几乎检测不到，尽管存在许多胶质细胞酸性蛋白免疫反应性星形胶质细胞形成胶质瘢痕。相比之下，强烈的PBR信号持续存在于小胶质细胞定位到损伤震中长达90天，尽管在7和90天之间的离子钙结合衔接子分子-1-阳性阿米巴样小胶质细胞的数量逐渐减少。体内正电子发射断层扫描成像最终支持了小胶质细胞中持久的PBR表达，并表明炎症组织损伤可能是可扩展的，除非它被星形胶质细胞瘢痕紧密密封。目前的研究结果共同支持的效用PBR在确定一个独特的时间模式的星形胶质细胞和小胶质细胞的激活，传统的胶质细胞标记物很难追求。(c)2007 Elsevier B. V.保留所有权利。
Elevated levels of peripheral benzodiazepine receptor (PBR) in glia have been documented in diverse nervous system injuries, while the identity and spatiotemporal characteristics of the cells showing upregulation of PBR remain elusive. We examined the astrocytic and microglial expressions of PBR in rat brains during the duration of ethanol-induced neuronal insults in order to clarify the significance of PBR as a biomarker capable of detecting a distinctive subpopulation of these glial cells involved in the impairment and protection of neurons. The levels of PBR, as determined by autoradiographic analysis using a specific radioligand, [C-11] DAA1106, began to significantly increase at 3 days after intrastriatal injection of ethanol, and peaked at 7 days. This was consistent with the results of double immunofluorescence staining and high-resolution emulsion autoradiography, which revealed upregulation of PBR in both microglia and astrocytes proliferating in nonoverlapping compartments of the injury site. Notably, increased expression of PBR in astrocytes was transiently observed in a manner parallel to the centripetal migration of these cells to the inflammatory lesion, which may be a response indispensable to the protection of intact tissue. Thereafter, astrocytic PBR was barely detectable, despite the presence of numerous glial fibrillary acidic protein-immunoreactive astrocytes forming glial scarring. By contrast, intense PBR signals were persistently present in microglia localized to the injury epicenter up to 90 days, notwithstanding a gradual reduction in the number of ionized calcium binding adapter molecule-1-positive amoeboid microglia between 7 and 90 days. The long-lasting PBR expression in microglia was finally supported by in vivo positron emission tomography imaging, and suggests that inflammatory tissue damage is potentially expandable unless it is tightly sealed by astrocytic scar. The present findings collectively support the utility of PBR in identifying a unique temporal pattern of astrocytic and microglial activation that conventional glial markers hardly pursue. (c) 2007 Elsevier B.V. All rights reserved.