title: Acute neuroinflammation in a clinically relevant focal cortical ischemic stroke model in rat: longitudinal positron emission tomography and immunofluorescent tracking.
abstract: Adequate estimation of neuroinflammatory processes following ischemic stroke is essential for better understanding of disease mechanisms, and for the development of treatment strategies. With the TSPO (18 kDa translocator protein) positron emission tomography (PET) radioligand [(11)C]PBR28, we monitored longitudinally the inflammatory response post-transient cerebral ischemia in rats, using a recently developed rat stroke model that produces isolated focal cortical infarcts with clinical relevance in size and pathophysiology. Six Sprague-Dawley rats were subjected to 90 min transient endovascular occlusion of the M2 segment of the middle cerebral artery (M2CAO). Animals were imaged with a nanoScan(®) PET/MRI system at 1, 4, 7 and 14 days after M2CAO with a bolus injection of [(11)C]PBR28. In the infarct region, we found a significantly increased uptake of [(11)C]PBR28 on day 4, 7 and 14 compared to day 1 as well as compared to the contralateral cortex. No significant increase was detected in the contralateral cortex during the 14 days of imaging. The activation in the infarct region gradually decreased between day 4 and day 14. In an additional group of animals (n = 26), immunofluorescence studies were performed with antibodies for activated microglia/monocytes (Cd11b), phagocytes (Cd68), astrocytes (glial fibrillary acidic protein) and TSPO. The TSPO immunofluorescence signal indicated reactive microgliosis post injury, corresponding to PET findings. The present clinically relevant animal model and TSPO PET ligand appear to be well suited for studies on neuroinflammation after ischemic stroke.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, 171 76, Stockholm, Sweden.
authors.forename: Miklós
authors.initials: M
authors.lastname: Tóth
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, 171 76, Stockholm, Sweden.|Department of Neuroradiology, Karolinska University Hospital, 171 76, Stockholm, Sweden.
authors.forename: Philip
authors.initials: P
authors.lastname: Little
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, 171 76, Stockholm, Sweden.|Department of Neuroradiology, Karolinska University Hospital, 171 76, Stockholm, Sweden.|Department of Radiology, Karolinska University Hospital, 171 76, Stockholm, Sweden.
authors.forename: Fabian
authors.initials: F
authors.lastname: Arnberg
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, 171 76, Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Häggkvist
authors.affiliation: Science for Life Laboratory, Department of Neuroscience, Karolinska Institutet, 17165, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Mulder
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, 171 76, Stockholm, Sweden.|Imperial College - NTU, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 639798, Singapore.
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, 171 76, Stockholm, Sweden. balazs.gulyas@ki.se.|Imperial College - NTU, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 639798, Singapore. balazs.gulyas@ki.se.|Imperial College London, Faculty of Medicine, Division of Brain Sciences, London, SW7 2AZ, UK. balazs.gulyas@ki.se.
authors.forename: Balázs
authors.initials: B
authors.lastname: Gulyás
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, 171 76, Stockholm, Sweden.|Department of Neuroradiology, Karolinska University Hospital, 171 76, Stockholm, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Holmin
mesh_terms: D000081:Acetamides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000000981:diagnostic imaging / Q000378:metabolism*; D005455:Fluorescent Antibody Technique / Q000379:methods; D057054:Molecular Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods; D011725:Pyridines / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D020521:Stroke / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: D000081:Acetamides; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; C526798:N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide; D011725:Pyridines; D011963:Receptors, GABA-A; C069997:Tspo protein, rat
keywords: M2CAO; Neuroinflammation; Positron emission tomography (PET); Rat; Stroke; [11C]PBR28