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The aim of this study was to investigate whether poststroke EE modulates chronic neuroinflammation and white matter pathology and how these changes relate to functional recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we investigated how EE influences the microglial response and myelin integrity during the recovery phase after photothrombotic stroke in male C57Bl\/6J mice. Mice were randomized by using a computer\u2010generated sequence into standard environment (SE) or EE housing conditions 2 days poststroke (SE:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096; EE:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097 for histological analyses; behavioral data unavailable for 2 SE mice). Sensorimotor performance was assessed at 7, 14, and 21 days poststroke using paw placement, foot fault, and limb symmetry tests, integrated into a composite Neuroscore. Housing in EE improved and sustained behavioral recovery up to 21 days. To explore whether specific microglial subpopulations are involved in tissue reorganization and functional outcome, immunofluorescence was performed for ionized calcium binding adaptor molecule 1 (Iba1), galectin\u20103 (Gal3), purinergic receptor P2Y12 (P2RY12), cluster of differentiation 68 (CD68), and triggering receptor expressed on myeloid cells 2 (TREM2), together with Black Gold myelin staining, in peri\u2010infarct and white matter regions. Statistical analyses included correlation analyses and analysis of covariance (ANCOVA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In SE mice, the inflammatory microglial marker Gal3 and the phagocytic marker CD68 correlated positively with infarct size (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.937,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006;\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.845,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.034, respectively), and the accumulation of myelin debris (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.865,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.026) together with loss of myelin coverage (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.907,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.013) followed lesion\u2010driven trajectories. By contrast, these correlations were absent in EE mice (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.028,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.953;\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.671,\n                      <jats:italic>p<\/jats:italic>\n                      =\u20090.099;\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.053,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.910;\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.292,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.525) indicating that enrichment attenuated lesion\u2010driven inflammatory responses and myelin damage. Importantly, Gal3 expression correlated specifically with peri\u2010infarct myelin debris (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.82,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.048), reinforcing its role as a pro\u2010inflammatory mediator. Finally, correlation analysis between Neuroscore and both microglial and myelin markers revealed a unique positive association between TREM2 coverage in white matter and improved Neuroscore in EE mice (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.890,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007; ANCOVA\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.039).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results support the idea that EE modulates processes of chronic post\u2010stroke inflammation, peri\u2010infarct myelin debris clearance and demyelination, and highlight white matter TREM2\u2010positive microglia as a potential cellular link to functional recovery.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/nep3.70028","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T14:58:06Z","timestamp":1772981886000},"page":"65-79","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Environmental enrichment modulates chronic poststroke inflammation and links white matter TREM2\u2010positive microglia in recovery in mice"],"prefix":"10.1002","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9417-9229","authenticated-orcid":false,"given":"Llu\u00eds","family":"Camprub\u00ed\u2010Ferrer","sequence":"first","affiliation":[{"name":"Experimental Neuroinflammation Laboratory, Department of Experimental Medical Sciences Lund University Lund Sk\u00e5ne Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6mer K.","family":"Kolbay","sequence":"additional","affiliation":[{"name":"Experimental Neuroinflammation Laboratory, Department of 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