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TSPO imaging in stroke: from animal models to human subjects

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Abstract

Stroke is a major health problem in developed countries and neuroinflammation has emerged over the last 2 decades as major contributor to the pathophysiological processes of brain damage following stroke. PET imaging of the translocator 18 kDa protein (TSPO) provides a unique non-invasive point of access to neuroinflammatory processes and more specifically microglial and astrocytic reaction after stroke in both animal models and patients. Here, we are reviewing both the experimental and clinical literature about in vivo TSPO PET and SPECT imaging in stroke. The studies in animal models of stroke reviewed here highlight a slightly faster time-course for TSPO expression in permanent vs. temporary stroke and a stronger activation in the infarct core in temporary stroke vs. a stronger activation in peri-infarct areas in permanent stroke. Altogether these findings suggest that areas where neuroinflammatory events occur post-stroke are at higher risk of secondary damage. The time-course of TSPO expression is slower in humans versus animal models of stroke. In human studies, the TSPO expression in the peri-infarct areas peaks 3–4 weeks after stroke and increased TSPO expression is demonstrated for months after the stroke in remote areas both ipsilesional to pyramidal tracts damage and in the contralesional hemisphere. Further clinical studies are warranted to address the role of TSPO and neuroinflammation in functional recovery and reorganization after stroke and the possible therapeutic implications. TSPO imaging appears to be a valid biomarker for demonstrating the dynamic process of neuroinflammation in stroke. But it is also clear that as the processes of microglial activation are increasingly complex, the need for new biomarkers and tracers targeting other aspect of glial reaction are needed to further investigate neuroinflammatory processes in patients.

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Acknowledgments

This work was financially supported by the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement HEALTH-F2-2011-278850 (INMiND), the Danish Council for Independent Research, the Research Committee of Rigshospitalet.

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Authors and Affiliations

  1. Wolfson Molecular Imaging Centre, Faculty of Medical and Human Sciences, University of Manchester, Manchester, M19 1GX, UK

    Hervé Boutin

  2. Neurobiology Research Unit, Department of Neurology, Rigshospitalet, 9 Blegdamsvej, 2100, Copenhagen, Denmark

    Lars H. Pinborg

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  1. Hervé Boutin
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  2. Lars H. Pinborg
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Correspondence to Lars H. Pinborg.

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Hervé Boutin and Lars H. Pinborg declare no conflicts of interest. The article contains data from studies with human and animal subjects performed by the authors of this article. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Boutin, H., Pinborg, L.H. TSPO imaging in stroke: from animal models to human subjects. Clin Transl Imaging 3, 423–435 (2015). https://doi.org/10.1007/s40336-015-0146-7

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