Imaging brain inflammation with [11C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats
| Autor: | Santiago Rojas, Vanessa Gómez, Maria J. Arranz, Deborah Pareto, Abraham Martín, Esther Verdaguer, Joan D. Gispert, Jesús Purroy, Jordi Llop, Anna M. Planas, Olga Millán, Ángel Chamorro |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Pathology medicine.medical_specialty Blotting Western Ischemia Inflammation Standardized uptake value Rats Sprague-Dawley Brain ischemia Lesion In vivo Image Processing Computer-Assisted medicine Animals RNA Messenger Receptor Cerebral Hemorrhage Focal ischemia business.industry Brain Cerebral Infarction Binding Isoquinolines Receptors GABA-A medicine.disease Benzodiazepine receptor subtypes Immunohistochemistry Rats Neurology Cerebral ischemia and/or reperfusion Ischemic Attack Transient Positron-Emission Tomography Reperfusion Injury Autoradiography Neurology (clinical) Radiopharmaceuticals medicine.symptom Cardiology and Cardiovascular Medicine business Ex vivo |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | [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. This work was supported by grants from the Comisión Interministerial de Ciencia y Tecnología (CICYT SAF2005-05793-CO2-01), Fondo de Investigaciones Sanitarias (FIS 2004-1104-O and PI051804-Red IM3), the European Network of Excellence DiMI (LSHB-CT-2005-512146), and Departament d'Unversitats, Recerca i Societat de la Generalitat de Catalunya – Beatriu de Pinós. AM and SR have PhD fellowships from FIS and Ministerio de Educación y Ciencia, respectively. |
| Databáze: | OpenAIRE |
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