{"id":3525,"date":"2025-09-12T21:29:26","date_gmt":"2025-09-12T12:29:26","guid":{"rendered":"https:\/\/misterx95.myds.me\/wordpress\/?p=3525"},"modified":"2025-09-12T21:31:18","modified_gmt":"2025-09-12T12:31:18","slug":"journal-club-2025-09-15","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=3525","title":{"rendered":"Journal Club 2025.09.15"},"content":{"rendered":"\n<p><em><strong>\u201cNote: Please use the DOI link to access the full article. Unfortunately, due to the file size, I am unable to upload the PDF. I apologize for the inconvenience, and thank you for your understanding.\u201d<\/strong><\/em><\/p>\n\n\n\n<h2><strong>A mast cell receptor mediates post-stroke brain inflammation via a dural-brain axis<\/strong><\/h2>\n\n\n\n<p><a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Ruchita&nbsp;Kothari<\/a><sup><a>1<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Mostafa W.&nbsp;Abdulrahim<\/a><sup><a>2<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Hyun Jong&nbsp;Oh<\/a><sup><a>1<\/a>,<a>9<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Daniel H.&nbsp;Capuzzi<\/a><sup><a>1<\/a>,<a>9<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Collin B.&nbsp;Kilgore<\/a><sup><a>1<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Sumil K.&nbsp;Nair<\/a><sup><a>2<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Yaowu&nbsp;Zhang<\/a><sup><a>2<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Nathachit&nbsp;Limjunyawong<\/a><sup><a>1<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Sarbjit S.&nbsp;Saini<\/a><sup><a>3<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Jennifer E.&nbsp;Kim<\/a><sup><a>4<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Justin M.&nbsp;Caplan<\/a><sup><a>2<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Fernanado L.&nbsp;Gonzalez<\/a><sup><a>2<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Christopher M.&nbsp;Jackson<\/a><sup><a>2<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Chetan&nbsp;Bettegowda<\/a><sup><a>2<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Judy&nbsp;Huang<\/a><sup><a>2<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Bhanu P.&nbsp;Ganesh<\/a><sup><a>5<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Chunfeng&nbsp;Tan<\/a><sup><a>5<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Raymond C.&nbsp;Koehler<\/a><sup><a>6<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Rafael J.&nbsp;Tamargo<\/a><sup><a>2<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Louise D.&nbsp;McCullough<\/a><sup><a>5<\/a><\/sup>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Risheng&nbsp;Xu<\/a><sup><a>2<\/a><\/sup>&nbsp;<a href=\"mailto:rxu4@jhmi.edu\">rxu4@jhmi.edu<\/a>&nbsp;\u2219&nbsp;<a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(25)00747-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425007470%3Fshowall%3Dtrue#\">Xinzhong&nbsp;Dong<\/a><sup><a>1<\/a>,<a>2<\/a>,<a>7<\/a>,<a>8<\/a>,<a>10<\/a><\/sup>&nbsp;<\/p>\n\n\n\n<p class=\"has-text-align-left\"><sup>1<\/sup>The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA <sup>2<\/sup>Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA <sup>3<\/sup>Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA <sup>4<\/sup>Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH 43210, USA<sup> 5<\/sup>Department of Neurology, The University of Texas Health Science Center Houston, McGovern Medical School, Houston, TX 77030, USA <sup>6<\/sup>Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA <sup>7<\/sup>Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA <sup>8<\/sup>Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA <sup>9<\/sup> These authors contributed equally <sup>10<\/sup>Lead contact<\/p>\n\n\n\n<p><strong>Publication History:<\/strong> Received December 20, 2024;&nbsp;Revised May 2, 2025;&nbsp;Accepted June 30, 2025;&nbsp;Published online July 24, 2025<\/p>\n\n\n\n<p>DOI:&nbsp;<a href=\"https:\/\/doi.org\/10.1016\/j.cell.2025.06.045\" target=\"_blank\" rel=\"noreferrer noopener\">10.1016\/j.cell.2025.06.045&nbsp;External Link<\/a>Also available on&nbsp;<a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0092867425007470\" target=\"_blank\" rel=\"noreferrer noopener\">ScienceDirect&nbsp;External Link<\/a><\/p>\n\n\n\n<p>Copyright: \u00a9 2025 The Author(s). Published by Elsevier Inc.<\/p>\n\n\n\n<p>User License:&nbsp;<a href=\"http:\/\/creativecommons.org\/licenses\/by\/4.0\/\" target=\"_blank\" rel=\"noreferrer noopener\">Creative Commons Attribution (CC BY 4.0)<\/a><\/p>\n\n\n\n<h2>Highlights<\/h2>\n\n\n\n<ul><\/ul>\n\n\n\n<ul>\n<li>Mrgprb2\/MRGPRX2 is a key receptor that activates meningeal mast cells after stroke<\/li>\n\n\n\n<li>Mrgprb2 regulates skull bone marrow neutrophil recruitment into the brain post-stroke<\/li>\n\n\n\n<li>Mast cell proteases cleave semaphorin, mediating neutrophil infiltration into the brain<\/li>\n\n\n\n<li>Inhibiting Mrgprb2 alleviates post-stroke brain inflammation and improves survival\n<ul><\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h2>Summary<\/h2>\n\n\n\n<p>The immune environment surrounding the brain plays a fundamental role in monitoring signs of injury. Insults, including ischemic stroke, can disrupt this balance and incite an exaggerated inflammatory response, yet the underlying mechanism remains unclear. Here, we show that the mast-cell-specific receptor Mrgprb2 regulates post-stroke brain inflammation from the meninges. Mrgprb2 causes meningeal mast cell degranulation after stroke, releasing immune mediators. This process recruits skull bone marrow neutrophils into the dura and further promotes neutrophil migration from the dura into the brain by cleaving the chemorepellent semaphorin 3a. We demonstrate that the human ortholog, MRGPRX2, is expressed in human meningeal mast cells and is activated by upregulation of the neuropeptide substance P following stroke. Pharmacologically inhibiting Mrgprb2 reduces post-stroke inflammation and improves neurological outcomes in mice, providing a druggable target. Collectively, our study identifies Mrgprb2 as a critical meningeal gatekeeper for immune migration from skull bone marrow reservoirs into the brain.<\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><a href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/09\/Graphical-Abstract.jpg\"><img decoding=\"async\" loading=\"lazy\" width=\"996\" height=\"996\" src=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/09\/Graphical-Abstract.jpg\" alt=\"\" class=\"wp-image-3526\" srcset=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/09\/Graphical-Abstract.jpg 996w, https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/09\/Graphical-Abstract-300x300.jpg 300w, https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/09\/Graphical-Abstract-150x150.jpg 150w, https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/09\/Graphical-Abstract-768x768.jpg 768w\" sizes=\"(max-width: 996px) 100vw, 996px\" \/><\/a><figcaption class=\"wp-element-caption\"><strong>Graphical Abstract<\/strong><\/figcaption><\/figure>\n","protected":false},"excerpt":{"rendered":"<p>\u201cNote: Please use the DOI link to access the full article. Unfortunately, due to the file size, I am unable to upload the PDF. I apologize for the inconvenience, and thank you for your understanding.\u201d A mast cell receptor mediates post-stroke brain inflammation via a dural-brain axis Ruchita&nbsp;Kothari1&nbsp;\u2219&nbsp;Mostafa W.&nbsp;Abdulrahim2&nbsp;\u2219&nbsp;Hyun Jong&nbsp;Oh1,9&nbsp;\u2219&nbsp;Daniel H.&nbsp;Capuzzi1,9&nbsp;\u2219&nbsp;Collin B.&nbsp;Kilgore1&nbsp;\u2219&nbsp;Sumil K.&nbsp;Nair2&nbsp;\u2219&nbsp;Yaowu&nbsp;Zhang2&nbsp;\u2219&nbsp;Nathachit&nbsp;Limjunyawong1&nbsp;\u2219&nbsp;Sarbjit S.&nbsp;Saini3&nbsp;\u2219&nbsp;Jennifer E.&nbsp;Kim4&nbsp;\u2219&nbsp;Justin [&hellip;]<\/p>\n","protected":false},"author":14,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}}},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3525"}],"collection":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/14"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3525"}],"version-history":[{"count":4,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3525\/revisions"}],"predecessor-version":[{"id":3530,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3525\/revisions\/3530"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3525"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3525"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3525"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}