{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:24:59Z","timestamp":1784042699116,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014220","name":"National Natural Science Foundation of China-Henan Joint Fund","doi-asserted-by":"publisher","award":["82071381"],"award-info":[{"award-number":["82071381"]}],"id":[{"id":"10.13039\/501100014220","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":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Post\u2010stroke depression represents a prevalent neuropsychiatric complication following intracerebral hemorrhage (ICH), yet its underlying mechanisms remain less understood compared to ischemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This translational investigation employed a multi\u2010omics approach, combining bioinformatics analysis of depression\u2010related (GSE214921) and ICH\u2010related (GSE18193) datasets from the GEO database with experimental validation. Using a collagenase\u2010induced striatal ICH murine model, we evaluated the effects of intranasal administration of osteopontin (OPN, encoded by SPP1) through neurobehavioral tests, histopathological evaluation, and molecular biology techniques.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Integrated bioinformatics analysis identified the SPP1 signaling pathway as a potential key regulator in post\u2010ICH depression pathogenesis. In\u00a0vivo, OPN treatment produced sustained neurobehavioral improvements at 28\u2009days post\u2010ICH, significantly ameliorating neurological deficits, mitigating anxiety\u2010depressive behaviors, and enhancing spatial learning\u2010memory performance. Histopathological evaluation revealed OPN's multifaceted neuroprotective effects, including attenuated hippocampal neuroinflammation, preserved Nissl body integrity, and restored dendritic arborization complexity. Mechanistically, OPN exerted its therapeutic effects through activation of the Nrf2\/BDNF signaling axis, as pharmacological inhibition of Nrf2 with ML385 completely abrogated both neuroprotection and BDNF upregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study is the first to demonstrate the critical role of SPP1 signaling in post\u2010ICH depression through modulation of the Nrf2\/BDNF pathway, providing novel therapeutic targets for clinical management of this debilitating neuropsychiatric sequela.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70680","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T04:15:56Z","timestamp":1764908156000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>SPP1<\/scp>\n                    \/\n                    <scp>OPN<\/scp>\n                    Alleviates Post\u2010Intracerebral Hemorrhage Depression and Cognitive Impairment via\n                    <scp>Nrf2<\/scp>\n                    \/\n                    <scp>BDNF<\/scp>\n                    Signaling Activation in Mice"],"prefix":"10.1002","volume":"31","author":[{"given":"Pengpeng","family":"Li","sequence":"first","affiliation":[{"name":"Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"},{"name":"Department of Neurosurgery Jiangnan University Medical Center  Wuxi Jiangsu China"},{"name":"Wuxi No. 2 People's Hospital, Affiliated Wuxi Clinical College of Nantong University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Gao","sequence":"additional","affiliation":[{"name":"Ningxia Medical University  Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqing","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Jiangnan University Medical Center  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengqian","family":"Mu","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"},{"name":"Department of Neurosurgery Jiangnan University Medical Center  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenxing","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Jiangnan University Medical Center  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"},{"name":"Wuxi 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