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    技術(shù)文章您現在的位置:首頁(yè) > 技術(shù)文章 > Cell: 腦缺血MCAO腦中風(fēng)Stroke造模品牌Doccol助力頂級期刊

    Cell: 腦缺血MCAO腦中風(fēng)Stroke造模品牌Doccol助力頂級期刊

    更新時(shí)間:2024-07-27   點(diǎn)擊次數:536次

    中文摘要:

    中風(fēng)的醫療負擔超出了腦損傷本身,很大程度上是由繼發(fā)性慢性合并癥決定的。我們假設這些合并癥可能有一個(gè)共同的免疫學(xué)原因,但中風(fēng)后對全身免疫的慢性影響尚未得到充分探索。在這里,我們將髓系先天免疫記憶確定為中風(fēng)后遠端器官功能障礙的原因。單細胞測序顯示,在腦損傷后長(cháng)達 3 個(gè)月的多個(gè)器官(尤其是心臟)中,單核細胞/巨噬細胞持續存在促炎變化,導致小鼠和中風(fēng)患者的心臟纖維化和功能障礙。IL-1β被確定為先天免疫記憶表觀(guān)遺傳變化的關(guān)鍵驅動(dòng)因素。這些變化可以移植到幼稚小鼠身上,誘發(fā)心功能障礙。通過(guò)中和中風(fēng)后的IL-1β或用CCR2/5抑制劑阻斷促炎性單核細胞運輸,我們預防了中風(fēng)后心功能不全。這種免疫靶向療法有可能預防各種IL-1β介導的合并癥,為二級預防免疫療法提供框架。

    英文摘要:

    The medical burden of stroke extends beyond the brain injury itself and is largely determined by chronic comorbidities that develop secondarily. We hypothesized that these comorbidities might share a common immunological cause, yet chronic effects post-stroke on systemic immunity are underexplored. Here, we identify myeloid innate immune memory as a cause of remote organ dysfunction after stroke. Single-cell sequencing revealed persistent pro-inflammatory changes in monocytes/macrophages in multiple organs up to 3 months after brain injury, notably in the heart, leading to cardiac fibrosis and dysfunction in both mice and stroke patients. IL-1β was identified as a key driver of epigenetic changes in innate immune memory. These changes could be transplanted to naive mice, inducing cardiac dysfunction. By neutralizing post-stroke IL-1β or blocking pro-inflammatory monocyte trafficking with a CCR2/5 inhibitor, we prevented post-stroke cardiac dysfunction. Such immune-targeted therapies could potentially prevent various IL-1β-mediated comorbidities, offering a framework for secondary prevention immunotherapy.


    論文信息:

    論文題目:Innate immune memory after brain injury drives inflammatory cardiac dysfunction

    期刊名稱(chēng):Cell

    時(shí)間期卷:在線(xiàn)2024-7-22pages685–700 (2024)

    在線(xiàn)時(shí)間:2024年7月22日


    研究亮點(diǎn):

    - 急性的腦缺血導致持續的先天免疫記憶

    - 先天免疫記憶導致慢性中風(fēng)后心功能不全

    - IL-1β通過(guò)表觀(guān)遺傳修飾誘導中風(fēng)后免疫

    - 阻斷 IL-1β 或單核細胞募集可預防心功能不全

    Cell: 腦缺血MCAO腦中風(fēng)Stroke造模品牌Doccol助力頂級期刊



    材料方法:

    Cell: 腦缺血MCAO腦中風(fēng)Stroke造模品牌Doccol助力頂級期刊



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