The Impact of Environmental Enrichment on Neurological Damage: Mechanistic Study of Ferroptosis Inhibition via Tlr4

The Impact of Environmental Enrichment on Neurological Damage: Mechanistic Study of Ferroptosis Inhibition via Tlr4 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Impact of Environmental Enrichment on Neurological Damage: Mechanistic Study of Ferroptosis Inhibition via Tlr4 Kai Li, Xingyu Zhang, Jichun Wu, Qian Li, Jianu Ni, Xia Bi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6855121/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Nov, 2025 Read the published version in Molecular Neurobiology → Version 1 posted 10 You are reading this latest preprint version Abstract Ischemic stroke, particularly cerebral ischemia/reperfusion injury, represents a significant global health challenge, leading to high rates of mortality and disability. This study investigates the neuroprotective effects of environmental enrichment (EE) following middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats, aiming to elucidate underlying molecular mechanisms. Employing a controlled experimental design, we observed that EE significantly reduced neuronal damage and improved functional recovery, as demonstrated through Nissl staining and Longa scale assessments. Gene expression analysis revealed 2,003 upregulated and 1,056 downregulated genes in the EE group compared to the MCAO group, with significant associations identified in pathways including the PI3K-Akt and MAPK signaling pathways, crucial for cell survival and apoptosis regulation. Additionally, histopathological analysis indicated enhanced neuronal integrity in the EE group. Notably, Tlr4 emerged as a key gene with differential expression, implicating its role in mediating ferroptosis. These findings underscore the potential of EE as a non-invasive therapeutic strategy for neuroprotection in ischemic stroke rehabilitation, highlighting the need for further investigation into its application in clinical settings. Future research should focus on the functional roles of identified differentially expressed genes and the development of targeted interventions that can mimic the beneficial effects of enriched environments. ischemic stroke enriched environment ferroptosis autophagy neuroprotection Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 20 Nov, 2025 Read the published version in Molecular Neurobiology → Version 1 posted Editorial decision: Revision requested 10 Aug, 2025 Reviews received at journal 10 Aug, 2025 Reviews received at journal 21 Jul, 2025 Reviewers agreed at journal 18 Jul, 2025 Reviewers agreed at journal 16 Jul, 2025 Reviewers agreed at journal 15 Jul, 2025 Reviewers invited by journal 14 Jul, 2025 Editor assigned by journal 08 Jul, 2025 Submission checks completed at journal 08 Jul, 2025 First submitted to journal 09 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6855121","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":485845079,"identity":"6cee3a16-9537-447a-ae6e-4f9abf8e6f14","order_by":0,"name":"Kai Li","email":"","orcid":"","institution":"Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kai","middleName":"","lastName":"Li","suffix":""},{"id":485845080,"identity":"c1b92da2-1e3e-4db6-b8ed-22e6f6e896b4","order_by":1,"name":"Xingyu Zhang","email":"","orcid":"","institution":"University of Traditional 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