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In Vivo Multimodal Imaging of Adenosine A2A Receptors in Neuroinflammation after Experimental Stroke

Maider Garbizu Albisu

Laboratory of Neuroimaging and Biomarkers of Inflammation, ACHUCARRO

11 Oct 2023 13:00

Aketxe Room, Sede Building, Leioa

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Adenosine receptors (ARs) are expressed in both the innate and adaptive immunity, suggesting a possible role in the neuroinflammatory response. Although the neuroprotective role of adenosine A1 receptors after ischemia has been already described, the role of other ARs such as adenosine A2A receptors (A2ARs) after ischemia remains unclear. Therefore, we aimed to analyse the expression of A2ARs in healthy and ischemic conditions and to evaluate their role in neuroinflammation using in vivo and ex vivo imaging techniques. Our results showed that in healthy conditions [11C]SCH442416-PET (Positron Emission Tomography) signal was mainly observed in the striatum. The images obtained by Magnetic Resonance Imaging (MRI) at day 1 showed a cortico-striatal infarction triggering a decrease of PET striatal signal, followed by a recovery at day 3 after stroke and a progressive decline. These results were confirmed by IHC analysis, showing a striatal increase of A2ARs+/CD11b+ cells at day 3 after stroke. Additionally, the rats treated with CGS21680, an agonist of A2ARs, obtained a higher striatal uptake of [18F]DPA-714 (a radiotracer to analyse neuroinflammation) accompanied by a higher number of TSPO+/CD11b+ cells at day 7 after stroke. Altogether, this study shows that A2ARs are mainly expressed in the striatum and demonstrates their involvement in the neuroinflammatory response after ischemic stroke.