{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:53:11Z","timestamp":1790823191521,"version":"4.1.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose\u2014<\/jats:title>\n                    <jats:p>Microglia are among the first cells to respond to intracerebral hemorrhage (ICH), but the mechanisms that underlie their activity following ICH remain unclear. IL (interleukin)-15 is a proinflammatory cytokine that orchestrates homeostasis and the intensity of the immune response following central nervous system inflammatory events. The goal of this study was to investigate the role of IL-15 in ICH injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods\u2014<\/jats:title>\n                    <jats:p>\n                      Using brain slices of patients with ICH, we determined the presence and cellular source of IL-15. A transgenic mouse line with targeted expression of IL-15 in astrocytes was generated to determine the role of astrocytic IL-15 in ICH. The expression of IL-15 was controlled by a glial fibrillary acidic protein promoter (GFAP-IL-15\n                      <jats:sup>tg<\/jats:sup>\n                      ). ICH was induced by intraparenchymal injection of collagenase or autologous blood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results\u2014<\/jats:title>\n                    <jats:p>\n                      In patients with ICH and wild-type mice subjected to experimental ICH, we found a significant upregulation of IL-15 in astrocytes. In GFAP-IL-15\n                      <jats:sup>tg<\/jats:sup>\n                      mice, we found that astrocyte-targeted expression of IL-15 exacerbated brain edema and neurological deficits following ICH. This aggravated ICH injury in GFAP-IL-15\n                      <jats:sup>tg<\/jats:sup>\n                      mice is accompanied by increased microglial accumulation in close proximity to astrocytes in perihematomal tissues. Additionally, microglial expression of CD86, IL-1\u03b2, and TNF-\u03b1 is markedly increased in GFAP-IL-15\n                      <jats:sup>tg<\/jats:sup>\n                      mice following ICH. Furthermore, depletion of microglia using a colony stimulating factor 1 receptor inhibitor diminishes the exacerbation of ICH injury in GFAP-IL-15\n                      <jats:sup>tg<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>Our findings identify IL-15 as a mediator of the crosstalk between astrocytes and microglia that exacerbates brain injury following ICH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.119.028638","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T05:00:20Z","timestamp":1580878820000},"page":"967-974","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":108,"title":["IL (Interleukin)-15 Bridges Astrocyte-Microglia Crosstalk and Exacerbates Brain Injury Following Intracerebral Hemorrhage"],"prefix":"10.1161","volume":"51","author":[{"given":"Samuel X.","family":"Shi","sequence":"first","affiliation":[{"name":"From the Barrow Neurological Institute, St. Joseph\u2019s Hospital and Medical Center, Phoenix, AZ (S.X.S., K.S., K.W., A.F.D., Q.L.)"},{"name":"Interdisciplinary Graduate Program in Neuroscience, Arizona State University, Tempe (S.X.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix (Y.-J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaibin","family":"Shi","sequence":"additional","affiliation":[{"name":"From the Barrow Neurological Institute, St. Joseph\u2019s Hospital and Medical Center, Phoenix, AZ (S.X.S., K.S., K.W., A.F.D., Q.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristofer","family":"Wood","sequence":"additional","affiliation":[{"name":"From the Barrow Neurological Institute, St. Joseph\u2019s Hospital and Medical Center, Phoenix, AZ (S.X.S., K.S., K.W., A.F.D., Q.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F.","family":"Ducruet","sequence":"additional","affiliation":[{"name":"From the Barrow Neurological Institute, St. Joseph\u2019s Hospital and Medical Center, Phoenix, AZ (S.X.S., K.S., K.W., A.F.D., Q.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1828-4019","authenticated-orcid":false,"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Barrow Neurological Institute, St. Joseph\u2019s Hospital and Medical Center, Phoenix, AZ (S.X.S., K.S., K.W., A.F.D., 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