Abstract
Extracellular ATP released to the ischemic brain parenchyma is quickly metabolized by ectonucleotidases. Among them, the ecto-5’-nucleotidase CD73 encoded by Nt5e mediates the generation of immunosuppressive adenosine, constituting a potential therapeutic target to stop the inflammatory cascade. Genetic deletion of Nt5e led to increased infarct size in the murine photothrombotic stroke model. Therefore we aimed at validating the proposed protective function of CD73-derived adenosine using the intraluminal filament model for transient middle cerebral artery occlusion (tMCAO) that represents pathophysiological aspects of penumbra and reperfusion. Three days after tMACO, we did not detect a difference in stroke size measured by vital staining between CD73 deficient (CD73 –/–) and control mice. Consistent with this finding, CD73 –/– and control mice showed comparable numbers and composition of brain infiltrating leukocytes measured by flow cytometry. Using NanoString technology, we further demonstrated that CD73 –/– and control mice do not differ regarding glia cell gene expression profiles in whole brain mRNA on day three after tMCAO. Our findings highlight the potential impact of the selected experimental stroke model on study outcome and the need for cross-validation of originally promising immunomodulatory candidates.
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