{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:14:43Z","timestamp":1788448483740,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274656"],"award-info":[{"award-number":["82274656"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82575236"],"award-info":[{"award-number":["82575236"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Following ischemic stroke (IS), activated microglia activity could contribute to neuronal injury and blood\u2013brain barrier (BBB) disruption. The upstream vascular\u2010derived signal initiating this transition remains unclear; therefore, we investigated whether perivascular SPP1 regulates microglia\u2010mediated synapse engulfment during IS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male C57BL\/6 mice were assigned to sham, sh\n                      <jats:italic>Spp1<\/jats:italic>\n                      , middle cerebral artery occlusion\/reperfusion (MCAO\/R), and MCAO\/\n                      <jats:italic>R<\/jats:italic>\n                      \u2009+\u2009sh\n                      <jats:italic>Spp1<\/jats:italic>\n                      groups. Cerebral perfusion was assessed using laser speckle contrast imaging and super\u2010resolution vascular imaging, while neuronal injury was evaluated using Nissl and TUNEL staining. Proteomic profiling of the ischemic penumbra identified regulators of microglia\u2010mediated synaptic remodeling. Synaptic structure and glial\u2010vascular unit (GVU) integrity were examined using transmission electron microscopy, immunofluorescence, and molecular analyses. Behavioral outcomes were assessed using the open\u2010field, Barnes maze, rotarod, and wire\u2010hanging tests.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with sham controls, MCAO\/R mice displayed increased microglial synaptic engulfment and ultrastructural synaptic damage in the ischemic penumbra, accompanied by reduced synaptic protein expression. Proteomic analysis revealed upregulation of inflammatory and vascular\u2010related pathways, with marked upregulation of SPP derived from perivascular macrophages.\n                      <jats:italic>Spp1<\/jats:italic>\n                      silencing attenuated neuroinflammation, reduced infarct volume, improved cerebral perfusion, preserved GVU integrity, and alleviated behavioral deficits.\n                      <jats:italic>Spp1<\/jats:italic>\n                      suppression also reduced microglial synaptic engulfment in\u00a0vivo and restored synaptic protein and mRNA levels in\u00a0vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Targeting perivascular SPP1 suppresses excessive microglia\u2010mediated synaptic engulfment, preserves BBB integrity and synaptic architecture, and offers a GVU\u2010centered therapeutic strategy for IS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70886","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T08:55:47Z","timestamp":1777366547000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Perivascular\n                    <scp>SPP1<\/scp>\n                    Drives Microglial Synaptic Engulfment After Ischemic Stroke"],"prefix":"10.1002","volume":"32","author":[{"given":"Chenchen","family":"Xu","sequence":"first","affiliation":[{"name":"Institute of Neurology Anhui University of Chinese Medicine  Hefei China"},{"name":"Wannan Medical College  Wuhu China"},{"name":"The Affiliated Hospital of Institute of Neurology Anhui University of Chinese Medicine  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Neurology Anhui University of Chinese Medicine  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Neurology Anhui University of Chinese Medicine  Hefei China"},{"name":"The Affiliated Hospital of Institute of Neurology Anhui University of Chinese Medicine  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3020-0245","authenticated-orcid":false,"given":"Rui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Neurology Anhui University of Chinese Medicine  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Neurology Anhui University of Chinese Medicine  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Xia","sequence":"additional","affiliation":[{"name":"Institute of Neurology Anhui University 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