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01-04-2016 | Original Article

Acute neuroinflammation in a clinically relevant focal cortical ischemic stroke model in rat: longitudinal positron emission tomography and immunofluorescent tracking

Authors: Miklós Tóth, Philip Little, Fabian Arnberg, Jenny Häggkvist, Jan Mulder, Christer Halldin, Balázs Gulyás, Staffan Holmin

Published in: Brain Structure and Function | Issue 3/2016

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 [¹¹C]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 [¹¹C]PBR28. In the infarct region, we found a significantly increased uptake of [¹¹C]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.

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Title: Acute neuroinflammation in a clinically relevant focal cortical ischemic stroke model in rat: longitudinal positron emission tomography and immunofluorescent tracking
Authors: Miklós Tóth
Philip Little
Fabian Arnberg
Jenny Häggkvist
Jan Mulder
Christer Halldin
Balázs Gulyás
Staffan Holmin
Publication date: 01-04-2016
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 3/2016
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-014-0970-y

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Acute neuroinflammation in a clinically relevant focal cortical ischemic stroke model in rat: longitudinal positron emission tomography and immunofluorescent tracking

Abstract

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