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在小鼠缺血/再灌注中风模型中，缺乏不会影响中风后的炎症和损伤大小。

deficiency does not affect post-stroke inflammation and lesion size in a murine ischemia/reperfusion stroke model.

作者信息

Schädlich Ines Sophie, Schnapauff Oliver, Pöls Lennart, Schrader Jürgen, Tolosa Eva, Rissiek Björn, Magnus Tim

机构信息

Department of Neurology, University Medical Centre Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg-Eppendorf, Germany.

Department of Molecular Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.

出版信息

iScience. 2022 May 26;25(6):104470. doi: 10.1016/j.isci.2022.104470. eCollection 2022 Jun 17.

DOI:10.1016/j.isci.2022.104470
PMID:35692634
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9184566/
Abstract

Extracellular ATP released to the ischemic brain parenchyma is quickly metabolized by ectonucleotidases. Among them, the ecto-5'-nucleotidase CD73 encoded by generates immunosuppressive adenosine. Genetic deletion of 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.

摘要

释放到缺血性脑实质的细胞外ATP会被胞外核苷酸酶迅速代谢。其中，由 编码的胞外5'-核苷酸酶CD73会生成具有免疫抑制作用的腺苷。在小鼠光血栓性中风模型中， 的基因缺失导致梗死面积增大。我们旨在使用代表半暗带和再灌注病理生理方面的短暂性大脑中动脉闭塞（tMCAO）中风模型来验证这一结果。tMACO后三天，我们未检测到CD73缺陷型（CD73 -/-）小鼠和对照小鼠之间的中风面积有差异。与此发现一致，通过流式细胞术测量，CD73 -/- 小鼠和对照小鼠脑内浸润白细胞的数量和组成相当。使用NanoString技术，我们进一步证明CD73 -/- 小鼠和对照小鼠在神经胶质细胞基因表达谱方面没有差异。我们的研究结果突出了中风模型对研究结果的潜在影响，以及对最初有前景的免疫调节候选物进行交叉验证的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dc/9184566/bffc561f6b12/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dc/9184566/52552f7e6932/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dc/9184566/7d084ac7ea36/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dc/9184566/1e10679dce7f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dc/9184566/bffc561f6b12/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dc/9184566/52552f7e6932/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dc/9184566/7d084ac7ea36/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dc/9184566/1e10679dce7f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dc/9184566/bffc561f6b12/gr3.jpg

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Unique Subtype of Microglia in Degenerative Thalamus After Cortical Stroke.皮层性脑卒中后丘脑变性中的独特小胶质细胞亚型。
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