{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T16:05:49Z","timestamp":1783181149598,"version":"3.54.6"},"reference-count":53,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":57,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VA","award":["I01 BX006534"],"award-info":[{"award-number":["I01 BX006534"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["25POST1372422"],"award-info":[{"award-number":["25POST1372422"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,15]]},"abstract":"<jats:p>\n                    Circulating monocyte-derived macrophages (MDM\u00f8) rapidly invade the brain after stroke, exerting both detrimental and beneficial effects. Elucidating mechanisms that mediate detrimental properties of MDM\u00f8 may identify therapeutic strategies to divert MDM\u00f8 from destructive phenotypes, while preserving their favorable effects. Toward this goal, the current study explores the function of Galectin-3 (GAL3) in MDM\u00f8 and elucidates mechanisms whereby MDM\u00f8-derived GAL3 exacerbates stroke injury. In the acutely injured brain, GAL3 expression was upregulated primarily within MDM\u00f8. Global KO of GAL3 reduced brain infarcts in the short term but did not sustain long-term positive outcomes. Using BM chimera mice, macrophage transplantation, and myeloid cell\u2013specific GAL3-KO (\n                    <jats:italic>LysM<\/jats:italic>\n                    <jats:sup>Cre+\/\u2013<\/jats:sup>\n                    <jats:italic>Lgals3<\/jats:italic>\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    ) mice, we demonstrated that GAL3 in MDM\u00f8 mediated acute infarct expansion after stroke. Coculturing brain lysate\u2013treated, BM-derived macrophages (BMDMs) with oxygen glucose deprivation\u2013challenged neurons induced neurotoxicity that was mitigated by the cell-permeable, selective GAL3 inhibitor TD139. GAL3 triggered cathepsin induction and lysosomal leakage in BMDMs, leading to inflammasome activation. Systemic and transient TD139 treatment in the acute injury phase reduced infarcts, tempered neuroinflammation, and improved long-term neurological outcomes. Therefore, MDM\u00f8-derived GAL3 represents a drug target that could be accessed in peripheral blood to potentially mitigate post-stroke brain injury.\n                  <\/jats:p>","DOI":"10.1172\/jci194139","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T17:00:50Z","timestamp":1771347650000},"source":"Crossref","is-referenced-by-count":1,"title":["Galectin-3 mediates lysosome-related inflammation within monocyte-derived macrophages in a mouse model of ischemic brain injury"],"prefix":"10.1172","volume":"136","author":[{"given":"Miao","family":"Wang","sequence":"first","affiliation":[{"name":"Geriatric Research Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 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