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Astrocytes, a major class of caretaker glia in the brain, can significantly alter outcomes after stroke through multiple pathways. Low\u2010density lipoprotein receptor\u2010related protein 1 (LRP1) is a multifunctional receptor that can modulate cellular signaling through its interaction with a diverse array of signaling mediators; however, its role in astrocyte function is not well elucidated. We tested whether LRP1 in astrocytes could alter outcomes in both the acute phase (24\u00a0h) and chronic phase (3\u20139 months) after middle cerebral artery occlusion in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Astrocyte\u2010specific\n                      <jats:italic>Lrp1<\/jats:italic>\n                      knockout mice were generated by crossing\n                      <jats:italic>\n                        Cx30\u2010CreER\n                        <jats:sup>T2<\/jats:sup>\n                      <\/jats:italic>\n                      mice with\n                      <jats:italic>Lrp1<\/jats:italic>\n                      \u2010floxed mice. As controls, mice were compared to\n                      <jats:italic>\n                        Cx30\u2010CreER\n                        <jats:sup>T2<\/jats:sup>\n                      <\/jats:italic>\n                      mice with wild\u2010type\n                      <jats:italic>Lrp1<\/jats:italic>\n                      . Cre activation was induced by tamoxifen treatment at 2 months of age in all mice. At 3 months of age, male and female mice were subjected to either middle cerebral artery occlusion for 1\u00a0h or sham surgery. Mice underwent motor coordination testing, and tissues were harvested at 24\u00a0h, 7 days, 3 months, or 9 months post\u2010surgery for subsequent histological analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      We found that genetic knockout of\n                      <jats:italic>Lrp1<\/jats:italic>\n                      in astrocytes worsened motor coordination in mice acutely after middle cerebral artery occlusion, but paradoxically improved long\u2010term outcomes by 3 months after stroke. Notably, at 3 months post\u2010stroke, loss of astrocyte LRP1 was associated with improved motor outcomes and reduced gliosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggest that loss of astrocyte LRP1 accelerates recovery after ischemic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71300","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T10:13:14Z","timestamp":1774951994000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Knockout of Low\u2010Density Lipoprotein Receptor\u2010Related Protein 1 From Astrocytes in Adult Mice Accelerates Long\u2010Term Functional Recovery After Ischemic Stroke"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3798-6091","authenticated-orcid":false,"given":"Meng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery University of Texas Health Science Center  San Antonio Texas USA"},{"name":"South Texas Medical Scientist Training Program University of Texas Health Science Center  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8579-6372","authenticated-orcid":false,"given":"Sadiya N.","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery University of Texas Health Science Center  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery University of Texas Health Science Center  San Antonio Texas 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