{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T09:44:11Z","timestamp":1792575851048,"version":"4.5.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl. Stroke Res."],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1007\/s12975-026-01491-0","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T05:51:42Z","timestamp":1787377902000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Potential of NLRP3 Inhibitor MCC950 in Aging Mice Stroke Outcomes"],"prefix":"10.1007","volume":"17","author":[{"given":"Pradip K.","family":"Kamat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Badruzzaman","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahneela","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraar Dua","family":"Dua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanvi","family":"Divekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"David","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad A.","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanket","family":"Gavankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Hess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"1491_CR1","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1177\/17474930241308142","volume":"20","author":"VL Feigin","year":"2025","unstructured":"Feigin VL, Brainin M, Norrving B, et al. World Stroke Organization: global stroke fact sheet 2025. Int J Stroke. 2025;20:132\u201344.","journal-title":"Int J Stroke"},{"key":"1491_CR2","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1016\/S0140-6736(16)00163-X","volume":"387","author":"M Goyal","year":"2016","unstructured":"Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387:1723\u201331.","journal-title":"Lancet"},{"key":"1491_CR3","unstructured":"Savitz SI, Samaniego EA, Liebeskind DS, Boltze J, Participants SX. Updated priorities for cerebroprotection Trials. Stroke 2025."},{"key":"1491_CR4","doi-asserted-by":"publisher","first-page":"941","DOI":"10.5114\/aoms.2014.46214","volume":"10","author":"K Jaracz","year":"2014","unstructured":"Jaracz K, Grabowska-Fudala B, Gorna K, Kozubski W. Caregiving burden and its determinants in Polish caregivers of stroke survivors. Arch Med Sci. 2014;10:941\u201350.","journal-title":"Arch Med Sci"},{"key":"1491_CR5","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.pjnns.2014.07.004","volume":"48","author":"K Jaracz","year":"2014","unstructured":"Jaracz K, Grabowska-Fudala B, Gorna K, Kozubski W. Consequences of stroke in the light of objective and subjective indices: a review of recent literature. Neurol Neurochir Pol. 2014;48:280\u20136.","journal-title":"Neurol Neurochir Pol"},{"key":"1491_CR6","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.bbi.2020.12.009","volume":"92","author":"M Franke","year":"2021","unstructured":"Franke M, Bieber M, Kraft P, Weber ANR, Stoll G, Schuhmann MK. The NLRP3 inflammasome drives inflammation in ischemia\/reperfusion injury after transient middle cerebral artery occlusion in mice. Brain Behav Immun. 2021;92:223\u201333.","journal-title":"Brain Behav Immun"},{"key":"1491_CR7","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1186\/s12974-020-01879-1","volume":"17","author":"Y Chang","year":"2020","unstructured":"Chang Y, Zhu J, Wang D, et al. NLRP3 inflammasome-mediated microglial pyroptosis is critically involved in the development of post-cardiac arrest brain injury. J Neuroinflammation. 2020;17:219.","journal-title":"J Neuroinflammation"},{"key":"1491_CR8","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26083532","volume":"26","author":"M Gryka-Marton","year":"2025","unstructured":"Gryka-Marton M, Grabowska AD, Szukiewicz D. Breaking the barrier: the role of proinflammatory cytokines in BBB dysfunction. Int J Mol Sci. 2025;26:3532. https:\/\/doi.org\/10.3390\/ijms26083532.","journal-title":"Int J Mol Sci"},{"key":"1491_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02674-w","volume":"20","author":"M Bellut","year":"2023","unstructured":"Bellut M, Bieber M, Kraft P, Weber ANR, Stoll G, Schuhmann MK. Delayed NLRP3 inflammasome inhibition ameliorates subacute stroke progression in mice. J Neuroinflammation. 2023;20:4.","journal-title":"J Neuroinflammation"},{"key":"1491_CR10","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10040762","author":"M Bellut","year":"2022","unstructured":"Bellut M, Raimondi AT, Haarmann A, Zimmermann L, Stoll G, Schuhmann MK. NLRP3 inhibition reduces rt-PA induced endothelial dysfunction under ischemic conditions. Biomedicines. 2022;10:762. https:\/\/doi.org\/10.3390\/biomedicines10040762","journal-title":"Biomedicines"},{"key":"1491_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24350-x","volume":"8","author":"S Ismael","year":"2018","unstructured":"Ismael S, Zhao L, Nasoohi S, Ishrat T. Inhibition of the NLRP3-inflammasome as a potential approach for neuroprotection after stroke. Sci Rep. 2018;8:5971.","journal-title":"Sci Rep"},{"key":"1491_CR12","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/jcbfm.2013.242","volume":"34","author":"F Yang","year":"2014","unstructured":"Yang F, Wang Z, Wei X, et al. NLRP3 deficiency ameliorates neurovascular damage in experimental ischemic stroke. J Cereb Blood Flow Metab. 2014;34:660\u20137.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1491_CR13","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.1177\/0271678X20943823","volume":"40","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert N, Hurst V, Ahluwalia A, et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. J Cereb Blood Flow Metab. 2020;40:1769\u201377.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1491_CR14","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nm.3806","volume":"21","author":"RC Coll","year":"2015","unstructured":"Coll RC, Robertson AA, Chae JJ, et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 2015;21:248\u201355.","journal-title":"Nat Med"},{"key":"1491_CR15","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1016\/j.jhep.2017.01.022","volume":"66","author":"AR Mridha","year":"2017","unstructured":"Mridha AR, Wree A, Robertson AAB, et al. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice. J Hepatol. 2017;66:1037\u201346.","journal-title":"J Hepatol"},{"key":"1491_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2024.115067","volume":"384","author":"PK Kamat","year":"2025","unstructured":"Kamat PK, Khan MB, Siddiqui S, et al. Time of day dependent reduction in stroke infarct volume by the Reverb agonist SR9009 in mice. Exp Neurol. 2025;384:115067.","journal-title":"Exp Neurol"},{"key":"1491_CR17","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/s12975-023-01226-5","volume":"16","author":"PK Kamat","year":"2025","unstructured":"Kamat PK, Khan MB, Siddiqui S, et al. Time dimension influences severity of stroke and heightened immune response in mice. Transl Stroke Res. 2025;16:421\u201337.","journal-title":"Transl Stroke Res"},{"key":"1491_CR18","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1161\/STROKEAHA.121.038047","volume":"53","author":"PD Lyden","year":"2022","unstructured":"Lyden PD, Bosetti F, Diniz MA, et al. The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results. Stroke. 2022;53:1802\u201312.","journal-title":"Stroke"},{"key":"1491_CR19","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1161\/ATVBAHA.117.309575","volume":"37","author":"T van der Heijden","year":"2017","unstructured":"van der Heijden T, Kritikou E, Venema W, et al. NLRP3 inflammasome inhibition by MCC950 reduces atherosclerotic lesion development in apolipoprotein E-deficient mice-brief report. Arterioscler Thromb Vasc Biol. 2017;37:1457.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"1491_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2021.577543","author":"SX Huang","year":"2021","unstructured":"Huang SX, Chen Z, Fan BL, et al. A selective NLRP3 inflammasome inhibitor attenuates behavioral deficits and neuroinflammation in a mouse model of Parkinson\u2019s disease. J Neuroimmunol. 2021;354:577543 . https:\/\/doi.org\/10.1016\/j.jneuroim.2021.577543","journal-title":"J Neuroimmunol"},{"key":"1491_CR21","doi-asserted-by":"publisher","unstructured":"Lueptow LM. Novel object recognition test for the investigation of learning and memory in mice. Jove-J Vis Exp. 2017. https:\/\/doi.org\/10.3791\/55718.","DOI":"10.3791\/55718"},{"key":"1491_CR22","first-page":"113","volume":"36","author":"R Trueman","year":"2016","unstructured":"Trueman R. Everything you need to know about behavioral testing in rodent models of stroke. J Cerebr Blood F Met. 2016;36:113\u2013113.","journal-title":"J Cerebr Blood F Met"},{"key":"1491_CR23","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1007\/s12975-023-01124-w","volume":"15","author":"MB Khan","year":"2024","unstructured":"Khan MB, Alam H, Siddiqui S, et al. Exercise improves cerebral blood flow and functional outcomes in an experimental mouse model of vascular cognitive impairment and dementia (VCID). Transl Stroke Res. 2024;15:446\u201361.","journal-title":"Transl Stroke Res"},{"key":"1491_CR24","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1038\/aps.2017.103","volume":"38","author":"YL Liu","year":"2017","unstructured":"Liu YL, Xu ZM, Yang GY, et al. Sesamin alleviates blood-brain barrier disruption in mice with experimental traumatic brain injury. Acta Pharmacol Sin. 2017;38:1445\u201355.","journal-title":"Acta Pharmacol Sin"},{"key":"1491_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12041519","author":"CA Simmons","year":"2023","unstructured":"Simmons CA, Poupore N, Nathaniel TI. Age stratification and stroke severity in the telestroke network. J Clin Med. 2023;12:1519. https:\/\/doi.org\/10.3390\/jcm12041519","journal-title":"J Clin Med"},{"key":"1491_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2025.117861","volume":"183","author":"R Prakash","year":"2025","unstructured":"Prakash R, Waseem A, Siddiqui AJ, et al. MCC950 mitigates SIRT3-NLRP3-driven inflammation and rescues post-stroke neurogenesis. Biomed Pharmacother. 2025;183:117861.","journal-title":"Biomed Pharmacother"},{"key":"1491_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2022.137032","volume":"795","author":"X Wu","year":"2023","unstructured":"Wu X, Wang B, Zhou Y, et al. NLRP3 inflammasome inhibitor MCC950 reduces cerebral ischemia\/reperfusion induced neuronal ferroptosis. Neurosci Lett. 2023;795:137032.","journal-title":"Neurosci Lett"},{"key":"1491_CR28","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1007\/s12975-024-01319-9","volume":"16","author":"WM Zhu","year":"2025","unstructured":"Zhu WM, He XX, Huang DC, et al. Global and Regional Burden of Ischemic Stroke Disease from 1990 to 2021: An Age-Period-Cohort Analysis. Translational Stroke Res. 2025;16:1474\u201385.","journal-title":"Translational Stroke Res"},{"key":"1491_CR29","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.033341","author":"L Liu","year":"2024","unstructured":"Liu L, Zhao B, Yu YY, et al. Vascular aging in ischemic stroke. J Am Heart Assoc. 2024;13:e033341. https:\/\/doi.org\/10.1161\/JAHA.123.033341","journal-title":"J Am Heart Assoc"},{"key":"1491_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-57309-2","author":"JJ Liu","year":"2024","unstructured":"Liu JJ, Liu YY, Ma WJ, et al. Age-period-cohort analysis of ischemic stroke deaths attributable to physical inactivity in different income regions. Sci Rep. 2024;14:6547. https:\/\/doi.org\/10.1038\/s41598-024-57309-2.","journal-title":"Sci Rep"},{"key":"1491_CR31","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1097\/NNR.0000000000000703","volume":"73","author":"ZW Liu","year":"2024","unstructured":"Liu ZW, Zhang ZX, Wang JJ, et al. Depressive Symptoms in Young and Middle-Aged Stroke Patients. Nurs Res. 2024;73:149\u201357.","journal-title":"Nurs Res"},{"key":"1491_CR32","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1080\/13803395.2013.776009","volume":"35","author":"M Farinelli","year":"2013","unstructured":"Farinelli M, Panksepp J, Gestieri L, et al. Seeking and depression in stroke patients: an exploratory study. J Clin Exp Neuropsychol. 2013;35:348\u201358.","journal-title":"J Clin Exp Neuropsychol"},{"key":"1491_CR33","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1037\/pag0000824","volume":"39","author":"V Thorvaldsson","year":"2024","unstructured":"Thorvaldsson V, Skoog J, Skoog I, Johansson B. Impact of stroke on cognition in old age: comparison of two population-based cohorts, born up to 30 years apart and followed from age 70 to 85. Psychol Aging. 2024;39:484\u201394.","journal-title":"Psychol Aging"},{"key":"1491_CR34","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1055\/s-0035-1555115","volume":"36","author":"DL Murman","year":"2015","unstructured":"Murman DL. The impact of age on cognition. Semin Hear. 2015;36:111\u201321.","journal-title":"Semin Hear"},{"key":"1491_CR35","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.neuron.2014.12.032","volume":"85","author":"A Montagne","year":"2015","unstructured":"Montagne A, Barnes SR, Sweeney MD, et al. Blood-brain barrier breakdown in the aging human hippocampus. Neuron. 2015;85:296\u2013302.","journal-title":"Neuron"},{"key":"1491_CR36","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.2174\/1570159X18666200528143301","volume":"18","author":"T Okada","year":"2020","unstructured":"Okada T, Suzuki H, Travis ZD, Zhang JH. The stroke-induced blood-brain barrier disruption: current progress of inspection technique, mechanism, and therapeutic target. Curr Neuropharmacol. 2020;18:1187\u2013212.","journal-title":"Curr Neuropharmacol"},{"key":"1491_CR37","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1248970","volume":"14","author":"S Xue","year":"2023","unstructured":"Xue S, Zhou X, Yang ZH, Si XK, Sun X. Stroke-induced damage on the blood-brain barrier. Front Neurol. 2023;14:1248970. https:\/\/doi.org\/10.3389\/fneur.2023.1248970.","journal-title":"Front Neurol"},{"key":"1491_CR38","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1111\/cns.13221","volume":"25","author":"Y Toyota","year":"2019","unstructured":"Toyota Y, Wei J, Xi G, Keep RF, Hua Y. White matter T2 hyperintensities and blood-brain barrier disruption in the hyperacute stage of subarachnoid hemorrhage in male mice: The role of lipocalin-2. CNS Neurosci Ther. 2019;25:1207\u201314.","journal-title":"CNS Neurosci Ther"},{"key":"1491_CR39","doi-asserted-by":"publisher","first-page":"e00516","DOI":"10.1016\/j.neurot.2024.e00516","volume":"22","author":"S Sasannia","year":"2025","unstructured":"Sasannia S, Leigh R, Bastani PB, et al. Blood-brain barrier breakdown in brain ischemia: Insights from MRI perfusion imaging. Neurotherapeutics. 2025;22:e00516.","journal-title":"Neurotherapeutics"},{"key":"1491_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-29894-1","author":"S Sugiyama","year":"2023","unstructured":"Sugiyama S, Sasaki T, Tanaka H, et al. The tight junction protein occludin modulates blood-brain barrier integrity and neurological function after ischemic stroke in mice. Sci Rep. 2023. https:\/\/doi.org\/10.1038\/s41598-023-29894-1.","journal-title":"Sci Rep"},{"key":"1491_CR41","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112168","volume":"133","author":"LN Li","year":"2024","unstructured":"Li LN, Shi CL, Dong F, Xu GY, Lei MC, Zhang F. Targeting pyroptosis to treat ischemic stroke: from molecular pathways to treatment strategy. Int Immunopharmacol. 2024;133:112168. https:\/\/doi.org\/10.1016\/j.intimp.2024.112168.","journal-title":"Int Immunopharmacol"},{"key":"1491_CR42","doi-asserted-by":"publisher","unstructured":"Ismael S, Zhao L, Ishrat T. MCC950, a novel selective NLRP3-inflammasome inhibitor provides protection in a murine model of focal cerebral Ischemia. Stroke. 2018;49. https:\/\/doi.org\/10.1161\/str.49.suppl_1.WP94.","DOI":"10.1161\/str.49.suppl_1.WP94"},{"key":"1491_CR43","doi-asserted-by":"publisher","unstructured":"Hong P, Gu RN, Li FX, et al. NLRP3 inflammasome as a potential treatment in ischemic stroke concomitant with diabetes. J Neuroinflammation. 2019;16:121. https:\/\/doi.org\/10.1186\/s12974-019-1498-0.","DOI":"10.1186\/s12974-019-1498-0"},{"key":"1491_CR44","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9163521","author":"P Hong","year":"2018","unstructured":"Hong P, Li FX, Gu RN, et al. Inhibition of NLRP3 inflammasome ameliorates cerebral ischemia-reperfusion injury in diabetic mice. Neural Plast. 2018. https:\/\/doi.org\/10.1155\/2018\/9163521.","journal-title":"Neural Plast"}],"container-title":["Translational Stroke Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12975-026-01491-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12975-026-01491-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12975-026-01491-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T09:17:38Z","timestamp":1792574258000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12975-026-01491-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,22]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["1491"],"URL":"https:\/\/doi.org\/10.1007\/s12975-026-01491-0","relation":{},"ISSN":["1868-4483","1868-601X"],"issn-type":[{"value":"1868-4483","type":"print"},{"value":"1868-601X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,22]]},"assertion":[{"value":"8 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 August 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Clinical Trial Number","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"99"}}