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Título: | Imaging brain inflammation with [11C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats |
Autor: | Rojas, Santiago CSIC; Martín, Abraham; Arranz, Maria J.; Purroy, Jesús; Verdaguer, Esther CSIC; Planas, Anna M. CSIC ORCID | Palabras clave: | Cerebral ischemia and/or reperfusion Focal ischemia Binding Benzodiazepine receptor subtypes |
Fecha de publicación: | 2007 | Editor: | Nature Publishing Group | Citación: | Journal of Cerebral Blood Flow and Metabolism 27(12): 1975-1986 (2007) | Resumen: | [11C]PK11195 is used in positron emission tomography (PET) studies for imaging brain inflammation in vivo as it binds to the peripheral-type benzodiazepine receptor (PBR) expressed by reactive glia and macrophages. However, features of the cellular reaction required to induce a positive [11C]PK11195 signal are not well characterized. We performed [11C]PK11195 PET and autoradiography in rats after transient focal cerebral ischemia. We determined [3H]PK11195 binding and PBR expression in brain tissue and examined the lesion with several markers. [ 11C]PK11195 standard uptake value increased at day 4 and grew further at day 7 within the ischemic core. Accordingly, ex vivo [3H]PK11195 binding increased at day 4, and increases further at day 7. The PET signal also augmented in peripheral regions, but to a lesser extent than in the core. Binding in the region surrounding infarction was supported by [ 11C]PK11195 autoradiography at day 7 showing that the radioactive signal extended beyond the infarcted core. Enhanced binding was preceded by increases in PBR mRNA expression in the ipsilateral hemisphere, and a 18-kDa band corresponding to PBR protein was detected. Peripheral-type benzodiazepine receptor immunohistochemistry showed subsets of ameboid microglia/macrophages within the infarcted core showing a distinctive strong PBR expression from day 4. These cells were often located surrounding microhemorrhages. Reactive astrocytes forming a rim surrounding infarction at day 7 also showed some PBR immunostaining. These results show cellular heterogeneity in the level of PBR expression, supporting that PBR is not a simple marker of inflammation, and that the extent of [11C]PK11195 binding depends on intrinsic features of the inflammatory cells. © 2007 ISCBFM All rights reserved. | URI: | http://hdl.handle.net/10261/89381 | DOI: | 10.1038/sj.jcbfm.9600500 | Identificadores: | doi: 10.1038/sj.jcbfm.9600500 issn: 0271-678X e-issn: 1559-7016 |
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