1. ¹Department of Brain Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona (IIBB)-Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
2. ²Institut d'Alta Tecnología (IAT), Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, Spain
3. ³Stroke Unit, Institut Clínic de Malalties del Sistema Nerviós (ICMSN), Hospital Clínic, IDIBAPS, Barcelona, Spain

Correspondence: Dr AM Planas, Department of Pharmacology and Toxicology, Institut d'Investigacions Biomèdiques de Barcelona (IIBB)-Consejo Superior de Investigaciones Científicas (CSIC), Rosselló 161, planta 6, Barcelona E-08036, Spain. E-mail: ampfat@iibb.csic.es

Received 25 October 2006; Revised 13 March 2007; Accepted 13 March 2007; Published online 25 April 2007.

Abstract

[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.