https://m2.mtmt.hu/ hun 2026-09-21 01:32 JournalArticle 36076983 VALIDATED true Roland Patai, Krish Patel, Anna Csiszar, Zoltan Ungvari, and Adam Nyul-Toth contributed equally to this work. 0 false 2026-07-31T10:25:37.056+0000 2026-04-16T13:09:00.066+0000 2025-04-07T07:18:15.608+0000 true 10069606 Pintér Ibolya Katalin /api/admin/10069606 Admin Pintér Ibolya Katalin (SE_AOK_TranszlációsMedInt_Admin5_PI, admin) true 2026-07-31T10:24:16.721+0000 2025-06-25T11:44:37.050+0000 true 10074913 Sághi-Keszthelyi Anna /api/admin/10074913 Admin Sághi-Keszthelyi Anna (SE_KK_Admin5_SKA, admin) true Admin 10025544 /api/admin/10025544 Lévayné Deseő Katalin (MTMT Központi admin) Lévayné Deseő Katalin true 10025544 true 2026-06-09T18:52:41.774+0000 true false true 24 24 /api/publicationtype/24 PublicationType Folyóiratcikk 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType Folyóiratcikk 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType Szakcikk (Folyóiratcikk) 101 true 10000059 true 1 /api/category/1 Category Tudományos true 1 Patai, Roland true true /api/journal/10071822 REVIEWED GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) 2509-2715 2509-2723 true false 10071822 false 10071822 true 2509-2715 2509-2723 Journal FOREIGN 47 3 4871 4887 4871 17 2025 Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) contribute to vascular cognitive impairment and dementia (VCID), with aging and hypertension being key risk factors. Mitochondrial oxidative stress is a hallmark of cerebrovascular aging, leading to endothelial dysfunction. This study tests the hypothesis that increased mitochondrial oxidative stress contributes to age-related CMH susceptibility and evaluates the mitochondrial-targeted antioxidative peptide SS-31 (elamipretide) as a potential protective agent in an aged, hypertensive mouse model. Concurrently, we developed a high-throughput, machine learning–driven imaging pipeline to enhance CMH quantification and facilitate the screening of anti-aging vasoprotective interventions. To detect CMHs, brain sections were labeled with diaminobenzidine (DAB) and digitized using a slide scanner-based imaging platform. We developed multiple quantification tools, including color space transformation for enhanced contrast separation and a supervised machine-learning approach utilizing a random forest algorithm to generate whole-brain 3D reconstructions and precisely localize CMHs. We optimized a semi-automated detection method integrating color space transformation and machine learning, benchmarking it against traditional manual counting and color deconvolution-based approaches. While SS-31 treatment did not significantly mitigate hypertension-induced CMH burden in aged mice, our high-throughput imaging pipeline provided a reliable, scalable, and unbiased approach to CMH detection, reducing processing time while improving accuracy. This methodological advancement paves the way for future preclinical studies evaluating therapeutic strategies for cerebrovascular protection in aging. Our findings underscore the need for multi-targeted interventions to mitigate CMH-related neurovascular impairments and prevent VCID. Funding 2051813 /api/funding/2051813 (TKP2021-NKTA-47) false true Funding 2051814 /api/funding/2051814 (RRF-2.3.1-21-2022-00003) false true Funding 2051815 /api/funding/2051815 (EKÖP-2024–2) Támogató: New National Excellence Program false true true 2025 true true true false true false NONE 2026-07-31 false 12 0 12 8 5 12 12 12 12 12 12 8 8 8 4 0 12 8 12 8 0 28 28 Folyóiratcikk Journal Article 24 12 Könyvrészlet Chapter in Book 25 0 Könyv Book 23 0 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 0 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 0 0 0 Alkotás Achievement 22 0 0 0 Kutatási adat Research data 33 0 0 0 2025 0 6 5 6 5 2026 0 6 3 6 3 D1 false false false false 2025-06-24T11:44:33.906+0000 Doktori Iskola (SE); HUN-REN-SE Cerebrovaszkuláris és Neurokognitív ... (SE / AOK / I / KKI); Megelőző Orvostani és Népegészségtani Intézet (SE / AOK / I); Transzlációs Medicina Intézet (SE / AOK / I) 9 43 4 18 0 true 10025544 Language 10002 /api/language/10002 Angol Angol English true 2 true PersonAuthorship 126078371 /api/authorship/126078371 Patai, Roland 1 0.055555556 true false false Patai Roland true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078372 /api/authorship/126078372 Patel, Krish* 2 0.056 true false false Patel Krish true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078373 /api/authorship/126078373 Csik, Boglarka [Csík, Boglárka (Népegészségtan - ...), szerző] Megelőző Orvostani és Népegészségtani Intézet (SE / AOK / I) 3 0.056 false false false Author 10099172 /api/author/10099172 Csík Boglárka (Népegészségtan - öregedés, egészséges öregedés) Csík Boglárka true true Csik Boglarka true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078374 /api/authorship/126078374 Gulej, Rafal [Gulej, Rafal (Orvostudomány), szerző] Megelőző Orvostani és Népegészségtani Intézet (SE / AOK / I) 4 0.056 false false false Author 10092932 /api/author/10092932 Gulej Rafal (Orvostudomány) Gulej Rafal true true Gulej Rafal true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078375 /api/authorship/126078375 Nagaraja, Raghavendra Y. 5 0.055555556 false false false Nagaraja Raghavendra Y. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078376 /api/authorship/126078376 Nagy, Dorina 6 0.055555556 false false false Nagy Dorina true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078377 /api/authorship/126078377 Chandragiri, Siva Sai 7 0.055555556 false false false Chandragiri Siva Sai true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078378 /api/authorship/126078378 Shanmugarama, Santny 8 0.055555556 false false false Shanmugarama Santny true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078379 /api/authorship/126078379 Kordestan, Kiana Vali 9 0.055555556 false false false Kordestan Kiana Vali true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078380 /api/authorship/126078380 Nagykaldi, Mark 10 0.055555556 false false false Nagykaldi Mark true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078381 /api/authorship/126078381 Ekambaram, Shoba 11 0.055555556 false false false Ekambaram Shoba true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078382 /api/authorship/126078382 Ungvari, Anna ✉ [Ungvári, Anna Sára (népegészségtan), szerző] Megelőző Orvostani és Népegészségtani Intézet (SE / AOK / I) 12 0.056 false false true Author 10090858 /api/author/10090858 Ungvári Anna Sára (népegészségtan) Ungvári Anna Sára true true Ungvari Anna true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078383 /api/authorship/126078383 Yabluchanskiy, Andriy [Yabluchanskiy, Andriy (Orvostudomány), szerző] Megelőző Orvostani és Népegészségtani Intézet (SE / AOK / I) 13 0.056 false false false Author 10095385 /api/author/10095385 Yabluchanskiy Andriy (Orvostudomány) Yabluchanskiy Andriy true true Yabluchanskiy Andriy true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078384 /api/authorship/126078384 Tarantini, Stefano [Tarantini, Stefano (népegészségtan, g...), szerző] Megelőző Orvostani és Népegészségtani Intézet (SE / AOK / I) 14 0.056 false false false Author 10074557 /api/author/10074557 Tarantini Stefano (népegészségtan, gerontológia, molekuláris biológia, kórélettan) Tarantini Stefano true true Tarantini Stefano true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078385 /api/authorship/126078385 Benyo, Zoltan [Benyó, Zoltán (Élettan és kóréle...), szerző] Transzlációs Medicina Intézet (SE / AOK / I); HUN-REN-SE Cerebrovaszkuláris és Neurokognitív ... (SE / AOK / I / KKI) 15 0.056 false false false Author 10009921 /api/author/10009921 Benyó Zoltán (Élettan és kórélettan) Benyó Zoltán true 10009921 true Benyo Zoltan true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078386 /api/authorship/126078386 Csiszar, Anna** [Csiszar, Anna (Orvostudomany), szerző] Transzlációs Medicina Intézet (SE / AOK / I) 16 0.056 false true false Author 10071157 /api/author/10071157 Csiszar Anna (Orvostudomany) Csiszar Anna true true Csiszar Anna true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078387 /api/authorship/126078387 Ungvari, Zoltan** [Ungvári, Zoltán István (Orvostudomány, me...), szerző] Doktori Iskola (SE); Megelőző Orvostani és Népegészségtani Intézet (SE / AOK / I) 17 0.056 false true false Author 10043602 /api/author/10043602 Ungvári Zoltán István (Orvostudomány, megelőző orvostan, népegészségtan, kórélettan, gerontológia) Ungvári Zoltán István true 10043602 true Ungvari Zoltan true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126078388 /api/authorship/126078388 Nyul-Toth, Adam [Nyúl-Tóth, Ádám (biofizika), szerző] Megelőző Orvostani és Népegészségtani Intézet (SE / AOK / I) 18 0.056 false true false Author 10045003 /api/author/10045003 Nyúl-Tóth Ádám (biofizika) Nyúl-Tóth Ádám true 10045003 true Nyul-Toth Adam true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PublicationIdentifier 29203162 /api/publicationidentifier/29203162 DOI: 10.1007/s11357-025-01634-5 PlainSource 6 /api/publicationsource/6 DOI PublicationSourceType 10001 /api/publicationsourcetype/10001 DOI true true true DOI DOI https://doi.org/@@@ true true 6 true IDENTICAL 10.1007/s11357-025-01634-5 https://doi.org/10.1007/s11357-025-01634-5 false true PublicationIdentifier 29304402 /api/publicationidentifier/29304402 WoS: 001468076700001 PlainSource 1 /api/publicationsource/1 WoS PublicationSourceType 10003 /api/publicationsourcetype/10003 Indexelő adatbázis false true true WoS WoS https://www.webofscience.com/wos/woscc/full-record/@@@ true true 1 true IDENTICAL 001468076700001 https://www.webofscience.com/wos/woscc/full-record/001468076700001 true true PublicationIdentifier 29216175 /api/publicationidentifier/29216175 Scopus: 105001509428 PlainSource 3 /api/publicationsource/3 Scopus PublicationSourceType 10003 /api/publicationsourcetype/10003 Indexelő adatbázis false true true Scopus Scopus http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-@@@ true true 3 true IDENTICAL 105001509428 http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-105001509428 false true PublicationIdentifier 29223268 /api/publicationidentifier/29223268 PubMed: 40169521 PlainSource 17 /api/publicationsource/17 PubMed PublicationSourceType 10003 /api/publicationsourcetype/10003 Indexelő adatbázis false true true PubMed PubMed http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=@@@&dopt=Abstract true true 17 true IDENTICAL 40169521 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=40169521&dopt=Abstract true true PublicationIdentifier 31537088 /api/publicationidentifier/31537088 Egyéb URL: https://link.springer.com/10.1007/s11357-025-01634-5 PlainSource 40 /api/publicationsource/40 Egyéb URL PublicationSourceType 10006 /api/publicationsourcetype/10006 Link true true true Egyéb URL Other URL @@@ true true 40 true IDENTICAL https://link.springer.com/10.1007/s11357-025-01634-5 https://link.springer.com/10.1007/s11357-025-01634-5 false true PublicationIdentifier 31847150 /api/publicationidentifier/31847150 Egyéb URL: https://www.scopus.com/pages/publications/105001509428?origin=resultslist PlainSource 40 /api/publicationsource/40 Egyéb URL PublicationSourceType 10006 /api/publicationsourcetype/10006 Link true true true Egyéb URL Other URL @@@ true true 40 true NONE IDENTICAL https://www.scopus.com/pages/publications/105001509428?origin=resultslist https://www.scopus.com/pages/publications/105001509428?origin=resultslist false true SjrRating 11627782 /api/sjrrating/11627782 sjr:D1 (2025) Scopus - Veterinary (miscellaneous) GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) 2509-2715 2509-2723 2 0.0 journal RatingType 10002 /api/ratingtype/10002 sjr sjr true true ClassificationExternal 3401 /api/classificationexternal/3401 Scopus - Veterinary (miscellaneous) true 3401 true D1 DIRECT true true Reference 65231072 /api/reference/65231072 1. Akoudad S, Wolters FJ, Viswanathan A, de Bruijn RF, van der Lugt A, Hofman A, Koudstaal PJ, Ikram MA, Vernooij MW. Association of cerebral microbleeds with cognitive decline and dementia. JAMA Neurol. 2016;73:934–43. https://doi.org/10.1001/jamaneurol.2016.1017., DOI: 10.1001/jamaneurol.2016.1017 1 10.1001/jamaneurol.2016.1017 false true Reference 65231073 /api/reference/65231073 2. Qiu C, Cotch MF, Sigurdsson S, Jonsson PV, Jonsdottir MK, Sveinbjrnsdottir S, Eiriksdottir G, Klein R, Harris TB, van Buchem MA, Gudnason V, Launer LJ. Cerebral microbleeds, retinopathy, and dementia: the AGES-Reykjavik study. Neurology. 2010;75:2221–8. https://doi.org/10.1212/WNL.0b013e3182020349., DOI: 10.1212/WNL.0b013e3182020349 2 10.1212/WNL.0b013e3182020349 false true Reference 65231074 /api/reference/65231074 3. Werring DJ, Gregoire SM, Cipolotti L. Cerebral microbleeds and vascular cognitive impairment. J Neurol Sci. 2010;299:131–5. https://doi.org/10.1016/j.jns.2010.08.034., DOI: 10.1016/j.jns.2010.08.034 3 10.1016/j.jns.2010.08.034 false true Reference 65231075 /api/reference/65231075 4. Hainsworth AH, Markus HS, Schneider JA. Cerebral small vessel disease, hypertension, and vascular contributions to cognitive impairment and dementia. Hypertension. 2024;81:75–86. https://doi.org/10.1161/HYPERTENSIONAHA.123.19943., DOI: 10.1161/HYPERTENSIONAHA.123.19943 4 10.1161/HYPERTENSIONAHA.123.19943 false true Reference 65231076 /api/reference/65231076 5. Elahi FM, Wang MM, Meschia JF. Cerebral small vessel disease-related dementia: more questions than answers. Stroke. 2023;54:648–60. https://doi.org/10.1161/STROKEAHA.122.038265., DOI: 10.1161/STROKEAHA.122.038265 5 10.1161/STROKEAHA.122.038265 false true Reference 65231077 /api/reference/65231077 6. Ungvari Z, Tarantini S, Kirkpatrick AC, Csiszar A, Prodan CI. Cerebral microhemorrhages: mechanisms, consequences, and prevention. Am J Physiol Heart Circ Physiol. 2017;312:H1128–43. https://doi.org/10.1152/ajpheart.00780.2016., DOI: 10.1152/ajpheart.00780.2016 6 10.1152/ajpheart.00780.2016 false true Reference 65231078 /api/reference/65231078 7. Litak J, Mazurek M, Kulesza B, Szmygin P, Litak J, Kamieniak P, Grochowski C. Cerebral Small Vessel Disease. Int J Mol Sci. 2020;21. https://doi.org/10.3390/ijms21249729, DOI: 10.3390/ijms21249729 7 10.3390/ijms21249729 false true Reference 65231079 /api/reference/65231079 8. Kim BJ, Lee SH. Cerebral microbleeds: their associated factors, radiologic findings, and clinical implications. J Stroke. 2013;15:153–63. https://doi.org/10.5853/jos.2013.15.3.153., DOI: 10.5853/jos.2013.15.3.153 8 10.5853/jos.2013.15.3.153 false true Reference 65231080 /api/reference/65231080 9. Greenberg SM, Vernooij MW, Cordonnier C, Viswanathan A, Al-Shahi Salman R, Warach S, Launer LJ, Van Buchem MA, Breteler MM, Microbleed Study G. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol. 2009;8:165–74. https://doi.org/10.1016/S1474-4422(09)70013-4., DOI: 10.1016/S1474-4422(09)70013-4 9 10.1016/S1474-4422(09)70013-4 false true Reference 65231081 /api/reference/65231081 10. Duering M, Biessels GJ, Brodtmann A, Chen C, Cordonnier C, de Leeuw FE, Debette S, Frayne R, Jouvent E, Rost NS, Ter Telgte A, Al-Shahi Salman R, Backes WH, Bae HJ, Brown R, Chabriat H, De Luca A, deCarli C, Dewenter A, Doubal FN, Ewers M, Field TS, Ganesh A, Greenberg S, Helmer KG, Hilal S, Jochems ACC, Jokinen H, Kuijf H, Lam BYK, et al. Neuroimaging standards for research into small vessel disease-advances since 2013. Lancet Neurol. 2023;22:602–18. https://doi.org/10.1016/S1474-4422(23)00131-X., DOI: 10.1016/S1474-4422(23)00131-X 10 10.1016/S1474-4422(23)00131-X false true Reference 65231082 /api/reference/65231082 11. Greenberg SM, Bax F, van Veluw SJ. Amyloid-related imaging abnormalities: manifestations, metrics and mechanisms. Nat Rev Neurol. 2025. https://doi.org/10.1038/s41582-024-01053-8., DOI: 10.1038/s41582-024-01053-8 11 10.1038/s41582-024-01053-8 false true Reference 65231083 /api/reference/65231083 12. Fazekas F, Kleinert R, Roob G, Kleinert G, Kapeller P, Schmidt R, Hartung HP. Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds. AJNR Am J Neuroradiol. 1999;20:637–42. 12 false true Reference 65231084 /api/reference/65231084 13. Rosenberg GA, Wallin A, Wardlaw JM, Markus HS, Montaner J, Wolfson L, Iadecola C, Zlokovic BV, Joutel A, Dichgans M, Duering M, Schmidt R, Korczyn AD, Grinberg LT, Chui HC, Hachinski V. Consensus statement for diagnosis of subcortical small vessel disease. J Cereb Blood Flow Metab. 2016;36:6–25. https://doi.org/10.1038/jcbfm.2015.172., DOI: 10.1038/jcbfm.2015.172 13 10.1038/jcbfm.2015.172 false true Reference 65231085 /api/reference/65231085 14. Ungvari Z, Tarantini S, Hertelendy P, Valcarcel-Ares MN, Fulop GA, Logan S, Kiss T, Farkas E, Csiszar A, Yabluchanskiy A. Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence. Geroscience. 2017;39:33–42. https://doi.org/10.1007/s11357-017-9964-z., DOI: 10.1007/s11357-017-9964-z 14 10.1007/s11357-017-9964-z false true Reference 65231086 /api/reference/65231086 15. Rauchmann BS, Ghaseminejad F, Mekala S, Perneczky R. Alzheimer’s disease neuroimaging I. Cerebral microhemorrhage at MRI in mild cognitive impairment and early Alzheimer disease: association with tau and amyloid beta at PET imaging. Radiology. 2020;296:134–42. https://doi.org/10.1148/radiol.2020191904., DOI: 10.1148/radiol.2020191904 15 10.1148/radiol.2020191904 false true Reference 65231087 /api/reference/65231087 16. Oomens JE, van Gils V, Vos SJB, Freeze WM, Maserejian NN, Curiale G, Gillis C, Boada M, van der Flier WM, Hort J, Johnson SC, Lleo A, Ramakers IH, Rodrigue KM, Sanchez-Juan P, Sarazin M, Scarmeas N, Zetterberg H, Alcolea D, Barkhof F, Blennow K, Bottlaender M, den Braber A, Cerman J, Drake-Perez M, Fortea J, Handels R, Ingala S, Jimenez-Bonilla JF, Karavasilis S, et al. Cerebral microbleeds and amyloid pathology estimates from the amyloid biomarker study. JAMA Netw Open. 2025;8:e2455571. https://doi.org/10.1001/jamanetworkopen.2024.55571., DOI: 10.1001/jamanetworkopen.2024.55571 16 10.1001/jamanetworkopen.2024.55571 false true Reference 65231088 /api/reference/65231088 17. Nyul-Toth A, Tarantini S, Kiss T, Toth P, Galvan V, Tarantini A, Yabluchanskiy A, Csiszar A, Ungvari Z. Increases in hypertension-induced cerebral microhemorrhages exacerbate gait dysfunction in a mouse model of Alzheimer's disease. Geroscience. 2020. https://doi.org/10.1007/s11357-020-00256-3, DOI: 10.1007/s11357-020-00256-3 17 10.1007/s11357-020-00256-3 false true Reference 65231089 /api/reference/65231089 18. Toth P, Tarantini S, Springo Z, Tucsek Z, Gautam T, Giles CB, Wren JD, Koller A, Sonntag WE, Csiszar A, Ungvari Z. Aging exacerbates hypertension-induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection. Aging Cell. 2015;14:400–8. https://doi.org/10.1111/acel.12315., DOI: 10.1111/acel.12315 18 10.1111/acel.12315 false true Reference 65231090 /api/reference/65231090 19. Elmstahl S, Ellstrom K, Siennicki-Lantz A, Abul-Kasim K. Association between cerebral microbleeds and hypertension in the Swedish general population “Good Aging in Skane” study. J Clin Hypertens (Greenwich). 2019;21:1099–107. https://doi.org/10.1111/jch.13606., DOI: 10.1111/jch.13606 19 10.1111/jch.13606 false true Reference 65231091 /api/reference/65231091 20. Poels MM, Vernooij MW, Ikram MA, Hofman A, Krestin GP, van der Lugt A, Breteler MM. Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam scan study. Stroke. 2010;41:S103-106. https://doi.org/10.1161/STROKEAHA.110.595181., DOI: 10.1161/STROKEAHA.110.595181 20 10.1161/STROKEAHA.110.595181 false true Reference 65231092 /api/reference/65231092 21. Vernooij MW, van der Lugt A, Ikram MA, Wielopolski PA, Niessen WJ, Hofman A, Krestin GP, Breteler MM. Prevalence and risk factors of cerebral microbleeds: the Rotterdam scan study. Neurology. 2008;70:1208–14. https://doi.org/10.1212/01.wnl.0000307750.41970.d9., DOI: 10.1212/01.wnl.0000307750.41970.d9 21 10.1212/01.wnl.0000307750.41970.d9 false true Reference 65231093 /api/reference/65231093 22. Ding J, Sigurdsson S, Garcia M, Phillips CL, Eiriksdottir G, Gudnason V, van Buchem MA, Launer LJ. Risk factors associated with incident cerebral microbleeds according to location in older people: the age, gene/environment susceptibility (AGES)-Reykjavik study. JAMA Neurol. 2015;72:682–8. https://doi.org/10.1001/jamaneurol.2015.0174., DOI: 10.1001/jamaneurol.2015.0174 22 10.1001/jamaneurol.2015.0174 false true Reference 65231094 /api/reference/65231094 23. Miller LR, Tarantini S, Nyul-Toth A, Johnston MP, Martin T, Bullen EC, Bickel MA, Sonntag WE, Yabluchanskiy A, Csiszar A, Ungvari ZI, Elliott MH, Conley SM. Increased susceptibility to cerebral microhemorrhages is associated with imaging signs of microvascular degeneration in the retina in an insulin-like growth factor 1 deficient mouse model of accelerated aging. Front Aging Neurosci. 2022;14:788296. https://doi.org/10.3389/fnagi.2022.788296., DOI: 10.3389/fnagi.2022.788296 23 10.3389/fnagi.2022.788296 false true Reference 65231095 /api/reference/65231095 24. Faakye J, Nyul-Toth A, Muranyi M, Gulej R, Csik B, Shanmugarama S, Tarantini S, Negri S, Prodan C, Mukli P, Yabluchanskiy A, Conley S, Toth P, Csiszar A, Ungvari Z. Preventing spontaneous cerebral microhemorrhages in aging mice: a novel approach targeting cellular senescence with ABT263/navitoclax. Geroscience. 2024;46:21–37. https://doi.org/10.1007/s11357-023-01024-9., DOI: 10.1007/s11357-023-01024-9 24 10.1007/s11357-023-01024-9 false true Reference 65231096 /api/reference/65231096 25. Nyul-Toth A, Fulop GA, Tarantini S, Kiss T, Ahire C, Faakye JA, Ungvari A, Toth P, Toth A, Csiszar A, Ungvari Z. Cerebral venous congestion exacerbates cerebral microhemorrhages in mice. Geroscience. 2022;44:805–16. https://doi.org/10.1007/s11357-021-00504-0., DOI: 10.1007/s11357-021-00504-0 25 10.1007/s11357-021-00504-0 false true Reference 65231097 /api/reference/65231097 26. de Montgolfier O, Pincon A, Pouliot P, Gillis MA, Bishop J, Sled JG, Villeneuve L, Ferland G, Levy BI, Lesage F, Thorin-Trescases N, Thorin E. High systolic blood pressure induces cerebral microvascular endothelial dysfunction, neurovascular unit damage, and cognitive decline in mice. Hypertension. 2019;73:217–28. https://doi.org/10.1161/HYPERTENSIONAHA.118.12048., DOI: 10.1161/HYPERTENSIONAHA.118.12048 26 10.1161/HYPERTENSIONAHA.118.12048 false true Reference 65231098 /api/reference/65231098 27. Ungvari Z, Muranyi M, Gulej R, Negri S, Nyul-Toth A, Csik B, Patai R, Conley S, Milan M, Bagwell J, O'Connor D, Tarantini A, Yabluchanskiy A, Toth P, Csiszar A, Ungvari A, Mukli P, Tarantini S. Longitudinal detection of gait alterations associated with hypertension-induced cerebral microhemorrhages in mice: predictive role of stride length and stride time asymmetry and increased gait entropy. Geroscience. 2024. https://doi.org/10.1007/s11357-024-01210-3, DOI: 10.1007/s11357-024-01210-3 27 10.1007/s11357-024-01210-3 false true Reference 65231099 /api/reference/65231099 28. Thorin-Trescases N, Thorin E. Lifelong cyclic mechanical strain promotes large elastic artery stiffening: increased pulse pressure and old age-related organ failure. Can J Cardiol. 2016;32:624–33. https://doi.org/10.1016/j.cjca.2015.12.022., DOI: 10.1016/j.cjca.2015.12.022 28 10.1016/j.cjca.2015.12.022 false true Reference 65231100 /api/reference/65231100 29. Csiszar A, Ungvari A, Patai R, Gulej R, Yabluchanskiy A, Benyo Z, Kovacs I, Sotonyi P, Kirkpartrick AC, Prodan CI, Liotta EM, Zhang XA, Toth P, Tarantini S, Sorond FA, Ungvari Z. Atherosclerotic burden and cerebral small vessel disease: exploring the link through microvascular aging and cerebral microhemorrhages. Geroscience. 2024;46:5103–32. https://doi.org/10.1007/s11357-024-01139-7., DOI: 10.1007/s11357-024-01139-7 29 10.1007/s11357-024-01139-7 false true Reference 65231101 /api/reference/65231101 30. Faakye J, Nyul-Toth A, Gulej R, Csik B, Tarantini S, Shanmugarama S, Prodan C, Mukli P, Yabluchanskiy A, Conley S, Toth P, Csiszar A, Ungvari Z. Imaging the time course, morphology, neuronal tissue compression, and resolution of cerebral microhemorrhages in mice using intravital two-photon microscopy: insights into arteriolar, capillary, and venular origin. Geroscience. 2023. https://doi.org/10.1007/s11357-023-00839-w, DOI: 10.1007/s11357-023-00839-w 30 10.1007/s11357-023-00839-w false true Reference 65231102 /api/reference/65231102 31. Tarantini S, Yabluchanskiy A, Lindsey ML, Csiszar A, Ungvari Z. Effect of genetic depletion of MMP-9 on neurological manifestations of hypertension-induced intracerebral hemorrhages in aged mice. Geroscience. 2021;43:2611–9. https://doi.org/10.1007/s11357-021-00402-5., DOI: 10.1007/s11357-021-00402-5 31 10.1007/s11357-021-00402-5 false true Reference 65231103 /api/reference/65231103 32. Stankovics L, Ungvari A, Fekete M, Nyul-Toth A, Mukli P, Patai R, Csik B, Gulej R, Conley S, Csiszar A, Toth P. The vasoprotective role of IGF-1 signaling in the cerebral microcirculation: prevention of cerebral microhemorrhages in aging. Geroscience. 2024. https://doi.org/10.1007/s11357-024-01343-5, DOI: 10.1007/s11357-024-01343-5 32 10.1007/s11357-024-01343-5 false true Reference 65231104 /api/reference/65231104 33. Wakisaka Y, Chu Y, Miller JD, Rosenberg GA, Heistad DD. Critical role for copper/zinc-superoxide dismutase in preventing spontaneous intracerebral hemorrhage during acute and chronic hypertension in mice. Stroke. 2010;41:790–7. https://doi.org/10.1161/STROKEAHA.109.569616., DOI: 10.1161/STROKEAHA.109.569616 33 10.1161/STROKEAHA.109.569616 false true Reference 65231105 /api/reference/65231105 34. Wakisaka Y, Chu Y, Miller JD, Rosenberg GA, Heistad DD. Spontaneous intracerebral hemorrhage during acute and chronic hypertension in mice. J Cereb Blood Flow Metab. 2010;30:56–69. https://doi.org/10.1038/jcbfm.2009.183., DOI: 10.1038/jcbfm.2009.183 34 10.1038/jcbfm.2009.183 false true Reference 65231106 /api/reference/65231106 35. Tarantini S, Valcarcel-Ares NM, Yabluchanskiy A, Springo Z, Fulop GA, Ashpole N, Gautam T, Giles CB, Wren JD, Sonntag WE, Csiszar A, Ungvari Z. Insulin-like growth factor 1 deficiency exacerbates hypertension-induced cerebral microhemorrhages in mice, mimicking the aging phenotype. Aging Cell. 2017;16:469–79. https://doi.org/10.1111/acel.12583., DOI: 10.1111/acel.12583 35 10.1111/acel.12583 false true Reference 65231107 /api/reference/65231107 36. Faakye J, Nyul-Toth A, Muranyi M, Gulej R, Csik B, Shanmugarama S, Tarantini S, Negri S, Prodan C, Mukli P, Yabluchanskiy A, Conley S, Toth P, Csiszar A, Ungvari Z. Preventing spontaneous cerebral microhemorrhages in aging mice: a novel approach targeting cellular senescence with ABT263/navitoclax. Geroscience. 2023. https://doi.org/10.1007/s11357-023-01024-9, DOI: 10.1007/s11357-023-01024-9 36 10.1007/s11357-023-01024-9 false true Reference 65231108 /api/reference/65231108 37. Czigler A, Toth L, Szarka N, Berta G, Amrein K, Czeiter E, Lendvai-Emmert D, Bodo K, Tarantini S, Koller A, Ungvari Z, Buki A, Toth P. Hypertension exacerbates cerebrovascular oxidative stress induced by mild traumatic brain injury: protective effects of the mitochondria-targeted antioxidative peptide SS-31. J Neurotrauma. 2019;36:3309–15. https://doi.org/10.1089/neu.2019.6439., DOI: 10.1089/neu.2019.6439 37 10.1089/neu.2019.6439 false true Reference 65231109 /api/reference/65231109 38. Springo Z, Tarantini S, Toth P, Tucsek Z, Koller A, Sonntag WE, Csiszar A, Ungvari Z. Aging exacerbates pressure-induced mitochondrial oxidative stress in mouse cerebral arteries. J Gerontol A Biol Sci Med Sci. 2015;70:1355–9. https://doi.org/10.1093/gerona/glu244., DOI: 10.1093/gerona/glu244 38 10.1093/gerona/glu244 false true Reference 65231110 /api/reference/65231110 39. Dikalov SI, Ungvari Z. Role of mitochondrial oxidative stress in hypertension. Am J Physiol Heart Circ Physiol. 2013;305:H1417-1427. https://doi.org/10.1152/ajpheart.00089.2013., DOI: 10.1152/ajpheart.00089.2013 39 10.1152/ajpheart.00089.2013 false true Reference 65231111 /api/reference/65231111 40. Mikhed Y, Daiber A, Steven S. Mitochondrial oxidative stress, mitochondrial DNA damage and their role in age-related vascular dysfunction. Int J Mol Sci. 2015;16:15918–53. https://doi.org/10.3390/ijms160715918., DOI: 10.3390/ijms160715918 40 10.3390/ijms160715918 false true Reference 65231112 /api/reference/65231112 41. Guzik TJ, Touyz RM. Oxidative stress, inflammation, and vascular aging in hypertension. Hypertension. 2017;70:660–7. https://doi.org/10.1161/HYPERTENSIONAHA.117.07802., DOI: 10.1161/HYPERTENSIONAHA.117.07802 41 10.1161/HYPERTENSIONAHA.117.07802 false true Reference 65231113 /api/reference/65231113 42. Ungvari Z, Wolin MS, Csiszar A. Mechanosensitive production of reactive oxygen species in endothelial and smooth muscle cells: role in microvascular remodeling? Antioxid Redox Signal. 2006;8:1121–9., DOI: 10.1089/ars.2006.8.1121 42 10.1089/ars.2006.8.1121 false true Reference 65231114 /api/reference/65231114 43. Erdo F, Denes L, de Lange E. Age-associated physiological and pathological changes at the blood-brain barrier: a review. J Cereb Blood Flow Metab. 2017;37:4–24. https://doi.org/10.1177/0271678X16679420., DOI: 10.1177/0271678X16679420 43 10.1177/0271678X16679420 false true Reference 65231115 /api/reference/65231115 44. Wang Y, Wu J, Wang J, He L, Lai H, Zhang T, Wang X, Li W. Mitochondrial oxidative stress in brain microvascular endothelial cells: triggering blood-brain barrier disruption. Mitochondrion. 2023;69:71–82. https://doi.org/10.1016/j.mito.2023.01.007., DOI: 10.1016/j.mito.2023.01.007 44 10.1016/j.mito.2023.01.007 false true Reference 65231116 /api/reference/65231116 45. Andjelkovic AV, Situ M, Citalan-Madrid AF, Stamatovic SM, Xiang J, Keep RF. Blood-brain barrier dysfunction in normal aging and neurodegeneration: mechanisms, impact, and treatments. Stroke. 2023;54:661–72. https://doi.org/10.1161/STROKEAHA.122.040578., DOI: 10.1161/STROKEAHA.122.040578 45 10.1161/STROKEAHA.122.040578 false true Reference 65231117 /api/reference/65231117 46. Knox EG, Aburto MR, Clarke G, Cryan JF, O’Driscoll CM. The blood-brain barrier in aging and neurodegeneration. Mol Psychiatry. 2022;27:2659–73. https://doi.org/10.1038/s41380-022-01511-z., DOI: 10.1038/s41380-022-01511-z 46 10.1038/s41380-022-01511-z false true Reference 65231118 /api/reference/65231118 47. Sweeney MD, Kisler K, Montagne A, Toga AW, Zlokovic BV. The role of brain vasculature in neurodegenerative disorders. Nat Neurosci. 2018;21:1318–31. https://doi.org/10.1038/s41593-018-0234-x., DOI: 10.1038/s41593-018-0234-x 47 10.1038/s41593-018-0234-x false true Reference 65231119 /api/reference/65231119 48. Wilhelm I, Nyul-Toth A, Kozma M, Farkas AE, Krizbai IA. Role of pattern recognition receptors of the neurovascular unit in inflamm-aging. Am J Physiol Heart Circ Physiol. 2017;313:H1000–12. https://doi.org/10.1152/ajpheart.00106.2017., DOI: 10.1152/ajpheart.00106.2017 48 10.1152/ajpheart.00106.2017 false true Reference 65231120 /api/reference/65231120 49. Nagyoszi P, Nyul-Toth A, Fazakas C, Wilhelm I, Kozma M, Molnar J, Hasko J, Krizbai IA. Regulation of NOD-like receptors and inflammasome activation in cerebral endothelial cells. J Neurochem. 2015;135:551–64. https://doi.org/10.1111/jnc.13197., DOI: 10.1111/jnc.13197 49 10.1111/jnc.13197 false true Reference 65231121 /api/reference/65231121 50. Szeto HH, Birk AV. Serendipity and the discovery of novel compounds that restore mitochondrial plasticity. Clin Pharmacol Ther. 2014;96:672–83. https://doi.org/10.1038/clpt.2014.174., DOI: 10.1038/clpt.2014.174 50 10.1038/clpt.2014.174 false true Reference 65231122 /api/reference/65231122 51. Birk AV, Chao WM, Bracken C, Warren JD, Szeto HH. Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. Br J Pharmacol. 2014;171:2017–28. https://doi.org/10.1111/bph.12468., DOI: 10.1111/bph.12468 51 10.1111/bph.12468 false true Reference 65231123 /api/reference/65231123 52. Siegel MP, Kruse SE, Percival JM, Goh J, White CC, Hopkins HC, Kavanagh TJ, Szeto HH, Rabinovitch PS, Marcinek DJ. Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging Cell. 2013;12:763–71. https://doi.org/10.1111/acel.12102., DOI: 10.1111/acel.12102 52 10.1111/acel.12102 false true Reference 65231124 /api/reference/65231124 53. Dai DF, Hsieh EJ, Chen T, Menendez LG, Basisty NB, Tsai L, Beyer RP, Crispin DA, Shulman NJ, Szeto HH, Tian R, MacCoss MJ, Rabinovitch PS. Global proteomics and pathway analysis of pressure-overload-induced heart failure and its attenuation by mitochondrial-targeted peptides. Circ Heart Fail. 2013;6:1067–76. https://doi.org/10.1161/CIRCHEARTFAILURE.113.000406., DOI: 10.1161/CIRCHEARTFAILURE.113.000406 53 10.1161/CIRCHEARTFAILURE.113.000406 false true Reference 65231125 /api/reference/65231125 54. Birk AV, Liu S, Soong Y, Mills W, Singh P, Warren JD, Seshan SV, Pardee JD, Szeto HH. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol. 2013;24:1250–61. https://doi.org/10.1681/ASN.2012121216., DOI: 10.1681/ASN.2012121216 54 10.1681/ASN.2012121216 false true Reference 65231126 /api/reference/65231126 55. Szeto HH, Liu S, Soong Y, Wu D, Darrah SF, Cheng FY, Zhao Z, Ganger M, Tow CY, Seshan SV. Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury. J Am Soc Nephrol. 2011;22:1041–52. https://doi.org/10.1681/ASN.2010080808., DOI: 10.1681/ASN.2010080808 55 10.1681/ASN.2010080808 false true Reference 65231127 /api/reference/65231127 56. Dai DF, Chen T, Szeto H, Nieves-Cintron M, Kutyavin V, Santana LF, Rabinovitch PS. Mitochondrial targeted antioxidant peptide ameliorates hypertensive cardiomyopathy. J Am Coll Cardiol. 2011;58:73–82. https://doi.org/10.1016/j.jacc.2010.12.044., DOI: 10.1016/j.jacc.2010.12.044 56 10.1016/j.jacc.2010.12.044 false true Reference 65231128 /api/reference/65231128 57. Cho S, Szeto HH, Kim E, Kim H, Tolhurst AT, Pinto JT. A novel cell-permeable antioxidant peptide, SS31, attenuates ischemic brain injury by down-regulating CD36. J Biol Chem. 2007;282:4634–42. https://doi.org/10.1074/jbc.M609388200., DOI: 10.1074/jbc.M609388200 57 10.1074/jbc.M609388200 false true Reference 65231129 /api/reference/65231129 58. Tarantini S, Valcarcel-Ares NM, Yabluchanskiy A, Fulop GA, Hertelendy P, Gautam T, Farkas E, Perz A, Rabinovitch PS, Sonntag WE, Csiszar A, Ungvari Z. Treatment with the mitochondrial-targeted antioxidant peptide SS-31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice. Aging Cell. 2018;17. https://doi.org/10.1111/acel.12731, DOI: 10.1111/acel.12731 58 10.1111/acel.12731 false true Reference 65231130 /api/reference/65231130 59. Nickel K, Zhu L, Mangalindan R, Snyder JM, Tucker M, Whitson J, Sweetwyne M, Valencia AP, Klug J, Jiang Z, Marcinek DJ, Rabinovitch P, Ladiges W. Long-term treatment with Elamipretide enhances healthy aging phenotypes in mice. Aging Pathobiol Ther. 2022;4:76–83. https://doi.org/10.31491/apt.2022.09.089., DOI: 10.31491/apt.2022.09.089 59 10.31491/apt.2022.09.089 false true Reference 65231131 /api/reference/65231131 60. Szeto HH, Liu S. Cardiolipin-targeted peptides rejuvenate mitochondrial function, remodel mitochondria, and promote tissue regeneration during aging. Arch Biochem Biophys. 2018;660:137–48. https://doi.org/10.1016/j.abb.2018.10.013., DOI: 10.1016/j.abb.2018.10.013 60 10.1016/j.abb.2018.10.013 false true Reference 65231132 /api/reference/65231132 61. Campbell MD, Duan J, Samuelson AT, Gaffrey MJ, Merrihew GE, Egertson JD, Wang L, Bammler TK, Moore RJ, White CC, Kavanagh TJ, Voss JG, Szeto HH, Rabinovitch PS, MacCoss MJ, Qian WJ, Marcinek DJ. Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice. Free Radic Biol Med. 2019;134:268–81. https://doi.org/10.1016/j.freeradbiomed.2018.12.031., DOI: 10.1016/j.freeradbiomed.2018.12.031 61 10.1016/j.freeradbiomed.2018.12.031 false true Reference 65231133 /api/reference/65231133 62. Patel N, Johnson MA, Vapniarsky N, Van Brocklin MW, Williams TK, Youngquist ST, Ford R, Ewer N, Neff LP, Hoareau GL. Elamipretide mitigates ischemia-reperfusion injury in a swine model of hemorrhagic shock. Sci Rep. 2023;13:4496. https://doi.org/10.1038/s41598-023-31374-5., DOI: 10.1038/s41598-023-31374-5 62 10.1038/s41598-023-31374-5 false true Reference 65231134 /api/reference/65231134 63. Miller LR, Bickel MA, Vance ML, Vaden H, Nagykaldi D, Nyul-Toth A, Bullen EC, Gautam T, Tarantini S, Yabluchanskiy A, Kiss T, Ungvari Z, Conley SM. Vascular smooth muscle cell-specific Igf1r deficiency exacerbates the development of hypertension-induced cerebral microhemorrhages and gait defects. Geroscience. 2024. https://doi.org/10.1007/s11357-024-01090-7, DOI: 10.1007/s11357-024-01090-7 63 10.1007/s11357-024-01090-7 false true Reference 65231135 /api/reference/65231135 64. Ungvari Z, Muranyi M, Gulej R, Negri S, Nyul-Toth A, Csik B, Patai R, Conley S, Milan M, Bagwell J, O’Connor D, Tarantini A, Yabluchanskiy A, Toth P, Csiszar A, Ungvari A, Mukli P, Tarantini S. Longitudinal detection of gait alterations associated with hypertension-induced cerebral microhemorrhages in mice: predictive role of stride length and stride time asymmetry and increased gait entropy. Geroscience. 2024;46:4743–60. https://doi.org/10.1007/s11357-024-01210-3., DOI: 10.1007/s11357-024-01210-3 64 10.1007/s11357-024-01210-3 false true Reference 65231136 /api/reference/65231136 65. Miller LR, Bickel MA, Vance ML, Vaden H, Nagykaldi D, Nyul-Toth A, Bullen EC, Gautam T, Tarantini S, Yabluchanskiy A, Kiss T, Ungvari Z, Conley SM. Vascular smooth muscle cell-specific Igf1r deficiency exacerbates the development of hypertension-induced cerebral microhemorrhages and gait defects. Geroscience. 2024;46:3481–501. https://doi.org/10.1007/s11357-024-01090-7., DOI: 10.1007/s11357-024-01090-7 65 10.1007/s11357-024-01090-7 false true Reference 65231137 /api/reference/65231137 66. Nyul-Toth A, Tarantini S, Kiss T, Toth P, Galvan V, Tarantini A, Yabluchanskiy A, Csiszar A, Ungvari Z. Increases in hypertension-induced cerebral microhemorrhages exacerbate gait dysfunction in a mouse model of Alzheimer’s disease. Geroscience. 2020;42:1685–98. https://doi.org/10.1007/s11357-020-00256-3., DOI: 10.1007/s11357-020-00256-3 66 10.1007/s11357-020-00256-3 false true Reference 65231138 /api/reference/65231138 67. Saks DG, Sachdev PS. Monogenic causes of cerebral small vessel disease- models for vascular cognitive impairment and dementia? Curr Opin Psychiatry. 2025;38:112–8. https://doi.org/10.1097/YCO.0000000000000978., DOI: 10.1097/YCO.0000000000000978 67 10.1097/YCO.0000000000000978 false true Reference 65231139 /api/reference/65231139 68. Pacella J, Lembo G, Carnevale L. A Translational perspective on the interplay between hypertension, inflammation and cognitive impairment. Can J Cardiol. 2024;40:2368–77. https://doi.org/10.1016/j.cjca.2024.10.015., DOI: 10.1016/j.cjca.2024.10.015 68 10.1016/j.cjca.2024.10.015 false true Reference 65231140 /api/reference/65231140 69. Toth P, Tarantini S, Csiszar A, Ungvari Z. Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging. Am J Physiol Heart Circ Physiol. 2017;312:H1–20. https://doi.org/10.1152/ajpheart.00581.2016., DOI: 10.1152/ajpheart.00581.2016 69 10.1152/ajpheart.00581.2016 false true Reference 65231141 /api/reference/65231141 70. Toth P, Tucsek Z, Sosnowska D, Gautam T, Mitschelen M, Tarantini S, Deak F, Koller A, Sonntag WE, Csiszar A, Ungvari Z. Age-related autoregulatory dysfunction and cerebromicrovascular injury in mice with angiotensin II-induced hypertension. J Cereb Blood Flow Metab. 2013;33:1732–42. https://doi.org/10.1038/jcbfm.2013.143., DOI: 10.1038/jcbfm.2013.143 70 10.1038/jcbfm.2013.143 false true Reference 65231142 /api/reference/65231142 71. Toth P, Tucsek Z, Tarantini S, Sosnowska D, Gautam T, Mitschelen M, Koller A, Sonntag WE, Csiszar A, Ungvari Z. IGF-1 deficiency impairs cerebral myogenic autoregulation in hypertensive mice. J Cereb Blood Flow Metab. 2014;34:1887–97. https://doi.org/10.1038/jcbfm.2014.156., DOI: 10.1038/jcbfm.2014.156 71 10.1038/jcbfm.2014.156 false true Reference 65231143 /api/reference/65231143 72. Toth P, Csiszar A, Tucsek Z, Sosnowska D, Gautam T, Koller A, Schwartzman ML, Sonntag WE, Ungvari Z. Role of 20-HETE, TRPC channels, and BKCa in dysregulation of pressure-induced Ca2+ signaling and myogenic constriction of cerebral arteries in aged hypertensive mice. Am J Physiol Heart Circ Physiol. 2013;305:H1698-1708. https://doi.org/10.1152/ajpheart.00377.2013., DOI: 10.1152/ajpheart.00377.2013 72 10.1152/ajpheart.00377.2013 false true Reference 65231144 /api/reference/65231144 73. Springo Z, Toth P, Tarantini S, Ashpole NM, Tucsek Z, Sonntag WE, Csiszar A, Koller A, Ungvari ZI. Aging impairs myogenic adaptation to pulsatile pressure in mouse cerebral arteries. J Cereb Blood Flow Metab. 2015;35:527–30. https://doi.org/10.1038/jcbfm.2014.256., DOI: 10.1038/jcbfm.2014.256 73 10.1038/jcbfm.2014.256 false true Reference 65231145 /api/reference/65231145 74. Finger CE, Moreno-Gonzalez I, Gutierrez A, Moruno-Manchon JF, McCullough LD. Age-related immune alterations and cerebrovascular inflammation. Mol Psychiatry. 2022;27:803–18. https://doi.org/10.1038/s41380-021-01361-1., DOI: 10.1038/s41380-021-01361-1 74 10.1038/s41380-021-01361-1 false true Reference 65231146 /api/reference/65231146 75. Wang HL, Zhang CL, Qiu YM, Chen AQ, Li YN, Hu B. Dysfunction of the blood-brain barrier in cerebral microbleeds: from bedside to bench. Aging Dis. 2021;12:1898–919. https://doi.org/10.14336/AD.2021.0514., DOI: 10.14336/AD.2021.0514 75 10.14336/AD.2021.0514 false true Reference 65231147 /api/reference/65231147 76. Li T, Huang Y, Cai W, Chen X, Men X, Lu T, Wu A, Lu Z. Age-related cerebral small vessel disease and inflammaging. Cell Death Dis. 2020;11:932. https://doi.org/10.1038/s41419-020-03137-x., DOI: 10.1038/s41419-020-03137-x 76 10.1038/s41419-020-03137-x false true Reference 65231148 /api/reference/65231148 77. Chiao YA, Zhang H, Sweetwyne M, Whitson J, Ting YS, Basisty N, Pino LK, Quarles E, Nguyen NH, Campbell MD, Zhang T, Gaffrey MJ, Merrihew G, Wang L, Yue Y, Duan D, Granzier HL, Szeto HH, Qian WJ, Marcinek D, MacCoss MJ, Rabinovitch P. Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice. Elife. 2020;9. https://doi.org/10.7554/eLife.55513, DOI: 10.7554/eLife.55513 77 10.7554/eLife.55513 false true Reference 65231149 /api/reference/65231149 78. Ungvari A, Gulej R, Patai R, Papp Z, Toth A, Szabo AA, Podesser BK, Sotonyi P, Benyo Z, Yabluchanskiy A, Tarantini S, Maier AB, Csiszar A, Ungvari Z. Sex-specific mechanisms in vascular aging: exploring cellular and molecular pathways in the pathogenesis of age-related cardiovascular and cerebrovascular diseases. Geroscience. 2025;47:301–37. https://doi.org/10.1007/s11357-024-01489-2., DOI: 10.1007/s11357-024-01489-2 78 10.1007/s11357-024-01489-2 false true /api/publication/36076983 Patai Roland et al. Aging, mitochondrial dysfunction, and cerebral microhemorrhages: a preclinical evaluation of SS-31 (elamipretide) and development of a high-throughput machine learning-driven imaging pipeline for cerebromicrovascular protection therapeutic screening. (2025) GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) 2509-2715 2509-2723 47 3 4871-4887<div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" >Patai Roland </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Patel Krish^* </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10099172"><a href="/gui2/?type=authors&mode=browse&sel=10099172" target="_blank">Csik Boglarka (<span class="authorship-author-name">Csík Boglárka</span> <span class="authorAux-mtmt"> Népegészségtan - öregedés, egészséges öregedés</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Megelőző Orvostani és Népegészségtani Intézet </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10092932"><a href="/gui2/?type=authors&mode=browse&sel=10092932" target="_blank">Gulej Rafal (<span class="authorship-author-name">Gulej Rafal</span> <span class="authorAux-mtmt"> Orvostudomány</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Megelőző Orvostani és Népegészségtani Intézet </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Nagaraja Raghavendra Y. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Nagy Dorina </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Chandragiri Siva Sai </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Shanmugarama Santny </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Kordestan Kiana Vali </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Nagykaldi Mark </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Ekambaram Shoba </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10090858"><a href="/gui2/?type=authors&mode=browse&sel=10090858" target="_blank">Ungvari Anna ✉ (<span class="authorship-author-name">Ungvári Anna Sára</span> <span class="authorAux-mtmt"> népegészségtan</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Megelőző Orvostani és Népegészségtani Intézet </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10095385"><a href="/gui2/?type=authors&mode=browse&sel=10095385" target="_blank">Yabluchanskiy Andriy (<span class="authorship-author-name">Yabluchanskiy Andriy</span> <span class="authorAux-mtmt"> Orvostudomány</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Megelőző Orvostani és Népegészségtani Intézet </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10074557"><a href="/gui2/?type=authors&mode=browse&sel=10074557" target="_blank">Tarantini Stefano (<span class="authorship-author-name">Tarantini Stefano</span> <span class="authorAux-mtmt"> népegészségtan, gerontológia, molekuláris bioló...</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Megelőző Orvostani és Népegészségtani Intézet </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10009921"><a href="/gui2/?type=authors&mode=browse&sel=10009921" target="_blank">Benyo Zoltan (<span class="authorship-author-name">Benyó Zoltán</span> <span class="authorAux-mtmt"> Élettan és kórélettan</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Transzlációs Medicina Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Klinikai Kórélettani Intézet">KKI</span>/HUN-REN-SE Cerebrovaszkuláris és Neurokognitív Betegségek Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10071157"><a href="/gui2/?type=authors&mode=browse&sel=10071157" target="_blank">Csiszar Anna^** (<span class="authorship-author-name">Csiszar Anna</span> <span class="authorAux-mtmt"> Orvostudomany</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Transzlációs Medicina Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10043602"><a href="/gui2/?type=authors&mode=browse&sel=10043602" target="_blank">Ungvari Zoltan^** (<span class="authorship-author-name">Ungvári Zoltán István</span> <span class="authorAux-mtmt"> Orvostudomány, megelőző orvostan, népegészségta...</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/Doktori Iskola; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Megelőző Orvostani és Népegészségtani Intézet </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10045003"><a href="/gui2/?type=authors&mode=browse&sel=10045003" target="_blank">Nyul-Toth Adam (<span class="authorship-author-name">Nyúl-Tóth Ádám</span> <span class="authorAux-mtmt"> biofizika</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Megelőző Orvostani és Népegészségtani Intézet </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;36076983" target="_blank">Aging, mitochondrial dysfunction, and cerebral microhemorrhages: a preclinical evaluation of SS-31 (elamipretide) and development of a high-throughput machine learning-driven imaging pipeline for cerebromicrovascular protection therapeutic screening</a></div> <div> <span class="journal-title">GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/2509-2715">2509-2715</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/2509-2723">2509-2723</a>)</span>: <span class="journal-volume">47</span> <span class="journal-issue">3</span> <span class="page"> pp 4871-4887 </span> <span class="year">(2025)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="10.1007/s11357-025-01634-5" target="_blank" href="https://doi.org/10.1007/s11357-025-01634-5"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="001468076700001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/001468076700001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="105001509428" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-105001509428"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="40169521" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=40169521&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="https://link.springer.com/10.1007/s11357-025-01634-5" target="_blank" href="https://link.springer.com/10.1007/s11357-025-01634-5"> Egyéb URL </a> </span> <span class="id identifier oa_NONE" title=" Nincs "> <a style="color:blue" title="https://www.scopus.com/pages/publications/105001509428?origin=resultslist" target="_blank" href="https://www.scopus.com/pages/publications/105001509428?origin=resultslist"> Egyéb URL </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Complementary and Alternative Medicine&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Geriatrics and Gerontology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Veterinary (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Aging&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Cardiology and Cardiovascular Medicine&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 12</span> | Független: 8 | Függő: 4 | Nem jelölt: 0 | WoS jelölt: 12 | Scopus jelölt:&nbsp;12 | WoS/Scopus jelölt:&nbsp;12 | DOI jelölt:&nbsp;12 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;36076983&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 28 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 36076983</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">kézi felvitel</span> </div> <div class="funder"> (TKP2021-NKTA-47), (RRF-2.3.1-21-2022-00003), (EKÖP-2024–2) Támogató: New National Excellence Program </div> <div class="lastModified">Utolsó módosítás: 2026.04.16. 15:09 Fi Tamás (SE_AOK_Nepegeszsegtan_Admin5_FT, admin) </div> <div class="lockedBy">Központi kezelésű 2026.06.09. 20:52 Lévayné Deseő Katalin (MTMT Központi admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Roland Patai, Krish Patel, Anna Csiszar, Zoltan Ungvari, and Adam Nyul-Toth contributed equally to this work.</pre> </div></div>