Nt5e deficiency does not affect post-stroke inflammation and lesion size in a murine ischemia/reperfusion stroke model
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Nt5e deficiency does not affect post-stroke inflammation and lesion size in a murine ischemia/reperfusion stroke model. / Schädlich, Ines Sophie; Schnapauff, Oliver; Pöls, Lennart; Schrader, Jürgen; Tolosa, Eva; Rissiek, Björn; Magnus, Tim.
in: ISCIENCE, Jahrgang 25, Nr. 6, 104470, 17.06.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Nt5e deficiency does not affect post-stroke inflammation and lesion size in a murine ischemia/reperfusion stroke model
AU - Schädlich, Ines Sophie
AU - Schnapauff, Oliver
AU - Pöls, Lennart
AU - Schrader, Jürgen
AU - Tolosa, Eva
AU - Rissiek, Björn
AU - Magnus, Tim
N1 - © 2022 The Author(s).
PY - 2022/6/17
Y1 - 2022/6/17
N2 - Extracellular ATP released to the ischemic brain parenchyma is quickly metabolized by ectonucleotidases. Among them, the ecto-5'-nucleotidase CD73 encoded by Nt5e generates immunosuppressive adenosine. Genetic deletion of Nt5e led to increased infarct size in the murine photothrombotic stroke model. We aimed at validating this result using the transient middle cerebral artery occlusion (tMCAO) stroke model that represents pathophysiological aspects of penumbra and reperfusion. Three days after tMACO, we did not detect a difference in stroke size 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. Our findings highlight the potential impact of stroke models on study outcome and the need for cross-validation of originally promising immunomodulatory candidates.
AB - Extracellular ATP released to the ischemic brain parenchyma is quickly metabolized by ectonucleotidases. Among them, the ecto-5'-nucleotidase CD73 encoded by Nt5e generates immunosuppressive adenosine. Genetic deletion of Nt5e led to increased infarct size in the murine photothrombotic stroke model. We aimed at validating this result using the transient middle cerebral artery occlusion (tMCAO) stroke model that represents pathophysiological aspects of penumbra and reperfusion. Three days after tMACO, we did not detect a difference in stroke size 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. Our findings highlight the potential impact of stroke models on study outcome and the need for cross-validation of originally promising immunomodulatory candidates.
U2 - 10.1016/j.isci.2022.104470
DO - 10.1016/j.isci.2022.104470
M3 - SCORING: Journal article
C2 - 35692634
VL - 25
JO - ISCIENCE
JF - ISCIENCE
SN - 2589-0042
IS - 6
M1 - 104470
ER -