Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 27, Issue 12, Pages 1975-1986Publisher
SAGE PUBLICATIONS INC
DOI: 10.1038/sj.jcbfm.9600500
Keywords
benzodiazepine receptor subtypes; binding; cerebral ischemia and/or reperfusion; focal ischemia; inflammation; PET imaging
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[C-11]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 [C-11] PK11195 signal are not well characterized. We performed [C-11] PK11195 PET and autoradiography in rats after transient focal cerebral ischemia. We determined [H-3]PK11195 binding and PBR expression in brain tissue and examined the lesion with several markers. [C-11] PK11195 standard uptake value increased at day 4 and grew further at day 7 within the ischemic core. Accordingly, ex vivo [H-3] 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 [C-11] 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 [C-11] PK11195 binding depends on intrinsic features of the inflammatory cells.
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