SPP1/OPN Alleviates Post-Intracerebral Hemorrhage Depression and Cognitive Impairment via Nrf2/BDNF Signaling Activation in Mice.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41345421", "kind": "science-record", "revision": 3, "content_hash": "sha256:eb665204e8a651f7c4ad5372ea7a93a8b217995076dfbcd2ad95d31b92a1050c", "created_at": "2026-11-01T20:31:21Z", "updated_at": "2026-11-01T22:15:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "SPP1/OPN Alleviates Post-Intracerebral Hemorrhage Depression and Cognitive Impairment via Nrf2/BDNF Signaling Activation in Mice.", "doi": "10.1002/cns.70680", "pmid": "41345421", "authors": ["Pengpeng Li", "Yangyang Gao", "Shiqing Du", "Zhengqian Mu", "Zhenxing Tao", "Xuqi Zhang", "Xudong Zhao"], "journal": "CNS neuroscience & therapeutics", "year": 2025, "abstract": "BACKGROUND: Post-stroke depression represents a prevalent neuropsychiatric complication following intracerebral hemorrhage (ICH), yet its underlying mechanisms remain less understood compared to ischemic stroke.\nMETHODS: This translational investigation employed a multi-omics approach, combining bioinformatics analysis of depression-related (GSE214921) and ICH-related (GSE18193) datasets from the GEO database with experimental validation. Using a collagenase-induced 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.\nRESULTS: Integrated bioinformatics analysis identified the SPP1 signaling pathway as a potential key regulator in post-ICH depression pathogenesis. In vivo, OPN treatment produced sustained neurobehavioral improvements at 28 days post-ICH, significantly ameliorating neurological deficits, mitigating anxiety-depressive behaviors, and enhancing spatial learning-memory 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.\nCONCLUSION: Our study is the first to demonstrate the critical role of SPP1 signaling in post-ICH depression through modulation of the Nrf2/BDNF pathway, providing novel therapeutic targets for clinical management of this debilitating neuropsychiatric sequela.", "claims": [{"id": "claim-method", "statement": "Mortality rates were compared using the chi‐squared test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41345421", "locator": "sections[22] \"Statistical Analysis\" paragraph 2", "quote": "Mortality rates were compared using the chi‐squared test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41345421", "locator": "sections[38] \"Data Availability Statement\" paragraph 2", "quote": "The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Although the OPN intervention group demonstrated a non‐significant reduction in mortality compared to the control cohort, this difference did not reach statistical significance (p > 0.05, Figure S1).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "Although the OPN intervention group demonstrated a non‐significant reduction in mortality compared to the control cohort, this difference did not reach statistical significance (p > 0.05, Figure S1)."}, "evidence": [{"asset": "source:pmid:41345421", "locator": "sections[25] \"Effect of OPN on Mortality After ICH\" paragraph 2", "quote": "Although the OPN intervention group demonstrated a non‐significant reduction in mortality compared to the control cohort, this difference did not reach statistical significance (p > 0.05, Figure S1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Although the OPN intervention group demonstrated a non‐significant reduction in mortality compared to the control cohort, this difference did not reach statistical significance (p > 0.05, Figure S1).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41345421"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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