Biphasic Oxygen-Regulating Cyanobacterial Hydrogel for Synergistic Ischemic Stroke Gas Therapy and Post-Stroke Depression Prevention

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Abstract

Abstract Ischemic stroke (87% of stroke cases) results from cerebral artery occlusion. Reperfusion therapy restores cerebral blood flow but predisposes to dual complications: ischemia-reperfusion injury (IRI) caused by oxygen fluctuations exacerbating neural damage and post-stroke depression (PSD). This study develops a cyanobacteria hydrogel composite (PT-CUCBD) for comprehensive reperfusion protection through precisely regulating the oxygen (O) microenvironment during distinct reperfusion phases. During pre-reperfusion phase, upconversion nanoparticles emit 660/450 nm light under 808 nm near-infrared irradiation for photosynthetic O production, thereby alleviating pre-reperfusion hypoxia, while ultraviolet light triggers nitric oxide (NO) release to promote angiogenesis. More importantly, during post-reperfusion phase, cessation of irradiation activates cyanobacterial respiration to deplete excess O, mitigating reoxygenation injury. Simultaneously, PT-CUCBD efficiently scavenges reactive oxygen species (ROS), while its loaded diallyl trisulfide releases hydrogen sulfide (HS) in response to glutathione to enhance neuroprotection. Furthermore, it promotes macrophage polarization toward the anti-inflammatory M2-type, suppressing neuroinflammation and apoptosis. Notably, experimental results demonstrate that, this multifunctional platform not only prevents IRI, but also significantly reduces the risk of PSD, establishing a promissing therapeutic paradigm for ischemic stroke.
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Biphasic Oxygen-Regulating Cyanobacterial Hydrogel for Synergistic Ischemic Stroke Gas Therapy and Post-Stroke Depression Prevention | 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 Biphasic Oxygen-Regulating Cyanobacterial Hydrogel for Synergistic Ischemic Stroke Gas Therapy and Post-Stroke Depression Prevention Haoxin Cheng, Haihua Yang, Hongmei Liu, Yihan Luo, Zhihao Zhou, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8221931/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Graphical Abstract Abstract Ischemic stroke (87% of stroke cases) results from cerebral artery occlusion. Reperfusion therapy restores cerebral blood flow but predisposes to dual complications: ischemia-reperfusion injury (IRI) caused by oxygen fluctuations exacerbating neural damage and post-stroke depression (PSD). This study develops a cyanobacteria hydrogel composite (PT-CUCBD) for comprehensive reperfusion protection through precisely regulating the oxygen (O) microenvironment during distinct reperfusion phases. During pre-reperfusion phase, upconversion nanoparticles emit 660/450 nm light under 808 nm near-infrared irradiation for photosynthetic O production, thereby alleviating pre-reperfusion hypoxia, while ultraviolet light triggers nitric oxide (NO) release to promote angiogenesis. More importantly, during post-reperfusion phase, cessation of irradiation activates cyanobacterial respiration to deplete excess O, mitigating reoxygenation injury. Simultaneously, PT-CUCBD efficiently scavenges reactive oxygen species (ROS), while its loaded diallyl trisulfide releases hydrogen sulfide (HS) in response to glutathione to enhance neuroprotection. Furthermore, it promotes macrophage polarization toward the anti-inflammatory M2-type, suppressing neuroinflammation and apoptosis. Notably, experimental results demonstrate that, this multifunctional platform not only prevents IRI, but also significantly reduces the risk of PSD, establishing a promissing therapeutic paradigm for ischemic stroke. ischemic stroke post-stroke depression near-infrared irradiation cyanobacteria upconversion nanoparticles Full Text Additional Declarations No competing interests reported. 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16:39:48","extension":"png","order_by":17,"title":"","display":"","copyAsset":false,"role":"graphical-abstract","size":68064,"visible":true,"origin":"","legend":"Ischemic stroke (87% of stroke cases) results from cerebral artery occlusion. Reperfusion therapy restores cerebral blood flow but predisposes to dual complications: ischemia-reperfusion injury (IRI) caused by oxygen fluctuations exacerbating neural damage and post-stroke depression (PSD). This study develops a cyanobacteria hydrogel composite (PT-CUCBD) for comprehensive reperfusion protection through precisely regulating the oxygen (O) microenvironment during distinct reperfusion phases. During pre-reperfusion phase, upconversion nanoparticles emit 660/450 nm light under 808 nm near-infrared irradiation for photosynthetic O production, thereby alleviating pre-reperfusion hypoxia, while ultraviolet light triggers nitric oxide (NO) release to promote angiogenesis. More importantly, during post-reperfusion phase, cessation of irradiation activates cyanobacterial respiration to deplete excess O, mitigating reoxygenation injury. Simultaneously, PT-CUCBD efficiently scavenges reactive oxygen species (ROS), while its loaded diallyl trisulfide releases hydrogen sulfide (HS) in response to glutathione to enhance neuroprotection. Furthermore, it promotes macrophage polarization toward the anti-inflammatory M2-type, suppressing neuroinflammation and apoptosis. Notably, experimental results demonstrate that, this multifunctional platform not only prevents IRI, but also significantly reduces the risk of PSD, establishing a promissing therapeutic paradigm for ischemic stroke.","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8221931/v1/642a0559ce62a2eb3f1d0129.png"},{"id":102962417,"identity":"c19b234c-1648-4a9e-9575-1496454c29af","added_by":"auto","created_at":"2026-02-19 04:08:18","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4831967,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8221931/v1_covered_af121440-baa6-4725-a97c-6c9cc0faeb65.pdf"},{"id":98427254,"identity":"82261c46-2c49-4231-91fb-93cacf5eb7de","added_by":"auto","created_at":"2025-12-17 16:40:02","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":8908509,"visible":true,"origin":"","legend":"","description":"","filename":"SupportingInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-8221931/v1/20eccdb5b47e7b66f0f49d0c.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Biphasic Oxygen-Regulating Cyanobacterial Hydrogel for Synergistic Ischemic Stroke Gas Therapy and Post-Stroke Depression Prevention","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"ischemic stroke, post-stroke depression, near-infrared irradiation, cyanobacteria, upconversion nanoparticles","lastPublishedDoi":"10.21203/rs.3.rs-8221931/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8221931/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Ischemic stroke (87% of stroke cases) results from cerebral artery occlusion. Reperfusion therapy restores cerebral blood flow but predisposes to dual complications: ischemia-reperfusion injury (IRI) caused by oxygen fluctuations exacerbating neural damage and post-stroke depression (PSD). This study develops a cyanobacteria hydrogel composite (PT-CUCBD) for comprehensive reperfusion protection through precisely regulating the oxygen (O) microenvironment during distinct reperfusion phases. During pre-reperfusion phase, upconversion nanoparticles emit 660/450 nm light under 808 nm near-infrared irradiation for photosynthetic O production, thereby alleviating pre-reperfusion hypoxia, while ultraviolet light triggers nitric oxide (NO) release to promote angiogenesis. More importantly, during post-reperfusion phase, cessation of irradiation activates cyanobacterial respiration to deplete excess O, mitigating reoxygenation injury. Simultaneously, PT-CUCBD efficiently scavenges reactive oxygen species (ROS), while its loaded diallyl trisulfide releases hydrogen sulfide (HS) in response to glutathione to enhance neuroprotection. Furthermore, it promotes macrophage polarization toward the anti-inflammatory M2-type, suppressing neuroinflammation and apoptosis. Notably, experimental results demonstrate that, this multifunctional platform not only prevents IRI, but also significantly reduces the risk of PSD, establishing a promissing therapeutic paradigm for ischemic stroke.","manuscriptTitle":"Biphasic Oxygen-Regulating Cyanobacterial Hydrogel for Synergistic Ischemic Stroke Gas Therapy and Post-Stroke Depression Prevention","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-12 03:35:36","doi":"10.21203/rs.3.rs-8221931/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4c445acf-09c2-4fc0-b8f7-65a6c550955f","owner":[],"postedDate":"December 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T10:00:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-12 03:35:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8221931","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8221931","identity":"rs-8221931","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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