{"id":107443,"date":"2025-05-13T18:11:07","date_gmt":"2025-05-13T22:11:07","guid":{"rendered":"https:\/\/med.virginia.edu\/cell-biology\/?p=107443"},"modified":"2025-05-15T11:38:42","modified_gmt":"2025-05-15T15:38:42","slug":"tet2-mediated-clonal-hematopoiesis-modestly-improves-neurological-deficits-and-is-associated-with-inflammation-resolution-in-the-subacute-phase-of-experimental-stroke","status":"publish","type":"post","link":"https:\/\/med.virginia.edu\/cell-biology\/2025\/05\/13\/tet2-mediated-clonal-hematopoiesis-modestly-improves-neurological-deficits-and-is-associated-with-inflammation-resolution-in-the-subacute-phase-of-experimental-stroke\/","title":{"rendered":"Tet2-mediated clonal hematopoiesis modestly improves neurological deficits and is associated with inflammation resolution in the subacute phase of experimental stroke"},"content":{"rendered":"<p><strong>UVA Author:<\/strong> Nicholas Chavkin<br \/>\n<strong>Citation:<\/strong> Evans MA, Chavkin NW, Sano S, Sun H, Sardana T, Ravi R, Doviak H, Wang Y, Yura Y, Polizio AH, Horitani K, Ogawa H, Hirschi KK, Walsh K. Tet2-mediated clonal hematopoiesis modestly improves neurological deficits and is associated with inflammation resolution in the subacute phase of experimental stroke. Front Cell Neurosci. 2024 Dec 17;18:1487867. doi: 10.3389\/fncel.2024.1487867. PMID: 39742155; PMCID: PMC11685025.<\/p>\n<p><strong>DOI:<\/strong> <a>https:\/\/doi.org\/10.3389\/fncel.2024.1487867<\/a><br \/>\n<strong>Pub-Med Number<\/strong>: 39742155<\/p>\n<hr \/>\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\n<p><strong class=\"sub-title\">Introduction:\u00a0<\/strong>Recent work has revealed that clonal hematopoiesis (CH) is associated with a higher risk of numerous age-related diseases, including ischemic stroke, however little is known about whether it influences stroke outcome independent of its widespread effects on cardiovascular disease. Studies suggest that leukocytes carrying CH driver mutations have an enhanced inflammatory profile, which could conceivably exacerbate brain injury after a stroke.<\/p>\n<p><strong class=\"sub-title\">Methods:\u00a0<\/strong>Using a competitive bone marrow transplant model of\u00a0<i>Tet2<\/i>-mediated CH, we tested the hypothesis that CH would lead to a poorer outcome after ischemic stroke by augmenting brain inflammation. Stroke was induced in mice by middle cerebral artery occlusion and neurological outcome was assessed at acute (24 h) and subacute (14 d) timepoints. Brains were collected at both time points for histological, immunofluorescence and gene expression assays.<\/p>\n<p><strong class=\"sub-title\">Results:\u00a0<\/strong>Unexpectedly,\u00a0<i>Tet2<\/i>-mediated CH had no effect on acute stroke outcome but led to a reduction in neurological deficits during the subacute phase. This improved neurological outcome was associated with lower levels of brain inflammation as evidenced by lower transcript levels of various inflammatory molecules alongside reduced astrogliosis.<\/p>\n<p><strong class=\"sub-title\">Discussion:\u00a0<\/strong>These findings suggest that\u00a0<i>Tet2<\/i>-mediated CH may have beneficial effects on outcome after stroke, contrasting with the conventional understanding of CH whereby leukocytes with driver mutations promote disease by exacerbating inflammation.<\/p>\n<\/div>\n<p><strong class=\"sub-title\">Keywords:\u00a0<\/strong>CHIP; TET2; cerebral ischemia; inflammation; ischemic stroke; mouse.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>UVA Author: Nicholas Chavkin Citation: Evans MA, Chavkin NW, Sano S, Sun H, Sardana T, Ravi R, Doviak H, Wang Y, Yura Y, Polizio AH, Horitani K, Ogawa H, Hirschi KK, Walsh K. Tet2-mediated clonal hematopoiesis modestly improves neurological deficits and is associated with inflammation resolution in the subacute phase of experimental stroke. Front Cell [&hellip;]<\/p>\n","protected":false},"author":1740,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[13],"tags":[],"class_list":["post-107443","post","type-post","status-publish","format-standard","hentry","category-featured-publications"],"acf":false,"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.1.1 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Tet2-mediated clonal hematopoiesis modestly improves neurological deficits and is associated with inflammation resolution in the subacute phase of experimental stroke - Department of Cell Biology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/med.virginia.edu\/cell-biology\/2025\/05\/13\/tet2-mediated-clonal-hematopoiesis-modestly-improves-neurological-deficits-and-is-associated-with-inflammation-resolution-in-the-subacute-phase-of-experimental-stroke\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Tet2-mediated clonal hematopoiesis modestly improves neurological deficits and is associated with inflammation resolution in the subacute phase of experimental stroke - Department of Cell Biology\" \/>\n<meta property=\"og:description\" content=\"UVA Author: Nicholas Chavkin Citation: Evans MA, Chavkin NW, Sano S, Sun H, Sardana T, Ravi R, Doviak H, Wang Y, Yura Y, Polizio AH, Horitani K, Ogawa H, Hirschi KK, Walsh K. Tet2-mediated clonal hematopoiesis modestly improves neurological deficits and is associated with inflammation resolution in the subacute phase of experimental stroke. 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