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.

释放到缺血性脑实质的细胞外 ATP 被外核苷酸酶快速代谢。其中，由Nt5e编码的外5'-核苷酸酶CD73产生免疫抑制腺苷。Nt5e的遗传缺失导致小鼠光血栓形成中风模型中梗塞面积增加。我们旨在使用代表半影和再灌注的病理生理学方面的瞬时大脑中动脉闭塞 (tMCAO) 中风模型来验证这一结果。tMACO 三天后，我们没有检测到 CD73 缺陷 (CD73 ^–/– ) 和对照小鼠之间的卒中大小差异。与这一发现一致，CD73 ^–/–和对照小鼠显示出通过流式细胞术测量的可比数量和组成的脑浸润白细胞。使用 NanoString 技术，我们进一步证明 CD73 ^–/–和对照小鼠在胶质细胞基因表达谱方面没有差异。我们的研究结果强调了卒中模型对研究结果的潜在影响，以及对最初有希望的免疫调节候选药物进行交叉验证的必要性。