Neuroinflammation extends brain tissue at risk to vital peri-infarct tissue: a double tracer [11C]PK11195-and [18F]FDG-PET study
Neuroinflammation extends brain tissue at risk to vital peri-infarct tissue: a double tracer [11C]PK11195-and [18F]FDG-PET study
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DOI：
10.1038/jcbfm.2009.36
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发表时间：
2009-06-01
影响因子：
6.3
通讯作者：
Graf, Rudolf
中科院分区：
文献类型：
--
作者：
Schroeter, Michael;Dennin, Maria A.;Graf, Rudolf
局灶性脑缺血引起强烈的炎症反应，包括驻留小胶质细胞的激活和单核/巨噬细胞的募集。这些细胞表达外周苯二氮卓类受体(PBRs)，并可通过使用[C-11]PK11195选择性结合PBRs的正电子发射断层扫描(PET)进行可视化。早期的研究表明，大鼠短暂性脑缺血导致梗死灶内[C-11]PK11195结合增加。在本研究中，我们研究了大鼠永久性脑缺血时PBRs的表达。采用大脑中动脉注射大分子球法建立永久性脑缺血模型。缺血后7天的多模式成像包括：(1)磁共振成像评估梗塞范围；(2)[F-18]-2-氟-2-脱氧-D-葡萄糖([F-18]FDG)-PET表征脑内葡萄糖的运输和代谢；(3)[C-11]PK11195-PET检测神经炎症。免疫组织化学证实了缺血损伤和神经炎症过程。与早期短暂性脑缺血相比，梗死灶中心未见[C-11]PK11195结合。相反，永久性缺血导致正常灌流的梗死区周围区[C-11]PK11195结合增加(平均标准摄取值(SUV)：1.93+/-0.49)，与激活的小胶质细胞和巨噬细胞共定位，[F-18]FDG代谢速率常数增加60%。这些结果表明，在永久性局灶性缺血后，在正常灌流的梗死区周围发生的神经炎症伴随着能量需求的增加，因此将处于危险中的组织延伸到梗死区附近。《脑血流与代谢杂志》(2009年)29期，1216-1225期；doi：10.1038/jcbfm.2009.36；在线出版
Focal cerebral ischemia elicits strong inflammatory responses involving activation of resident microglia and recruitment of monocytes/ macrophages. These cells express peripheral benzodiazepine receptors (PBRs) and can be visualized by positron emission tomography (PET) using [C-11]PK11195 that selectively binds to PBRs. Earlier research suggests that transient ischemia in rats induces increased [C-11] PK11195 binding within the infarct core. In this study, we investigated the expression of PBRs during permanent ischemia in rats. Permanent cerebral ischemia was induced by injection of macrospheres into the middle cerebral artery. Multimodal imaging 7 days after ischemia comprised (1) magnetic resonance imaging that assessed the extent of infarcts; (2) [F-18]-2-fluoro-2-deoxy-D-glucose ([F-18]FDG)-PET characterizing cerebral glucose transport and metabolism; and (3) [C-11]PK11195-PET detecting neuroinflammation. Immunohistochemistry verified ischemic damage and neuroinflammatory processes. Contrasting with earlier data for transient ischemia, no [C-11] PK11195 binding was found in the infarct core. Rather, permanent ischemia caused increased [C-11] PK11195 binding in the normoperfused peri-infarct zone (mean standard uptake value (SUV): 1.93 +/- 0.49), colocalizing with a 60% increase in the [F-18] FDG metabolic rate constant with accumulated activated microglia and macrophages. These results suggest that after permanent focal ischemia, neuroinflammation occurring in the normoperfused peri-infarct zone goes along with increased energy demand, therefore extending the tissue at risk to areas adjacent to the infarct. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1216-1225; doi:10.1038/jcbfm.2009.36; published online 8 April 2009