{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:29:18Z","timestamp":1793813358663,"version":"4.6.1"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100018936","name":"Universit\u00e4tsklinikum Heidelberg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018936","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Endothelial dysfunction is considered an emerging therapeutic target to prevent complications during acute stroke and to prevent recurrent stroke. This review aims to provide an overview of the current knowledge on endothelial dysfunction, outline the diagnostic methods used to measure it and highlight the drugs currently being investigated for the treatment of endothelial dysfunction in acute ischemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\u00a0The PubMed\u00ae and ClinicalTrials.gov electronic databases were searched for eligible articles\/studies dealing with endothelial dysfunction and stroke. The references of the articles were screened to identify additional sources. The data were abstracted and summarized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings and discussion<\/jats:title>\n                    <jats:p>Endothelial dysfunction can be measured by serum biomarkers as well as by ultrasound or plethysmography techniques. Drugs targeting endothelial dysfunction include widely used agents such as angiotensin-converting enzyme inhibitors or isosorbide mononitrate, but also experimental therapies such as endothelial progenitor cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The role of endothelial dysfunction in acute ischemic stroke has been studied increasingly in recent years. It has been shown that there is a correlation between endothelial dysfunction and parenchymal hematoma after endovascular thrombectomy. Also, early clinical trials are conducted investigating, e.g., endothelial progenitor cells in the treatment of endothelial dysfunction in ischemic stroke. Current research focuses on the integration of novel markers of endothelial dysfunction into routine clinical practice to support decision making in the treatment of acute ischemic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-025-12888-6","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T08:36:15Z","timestamp":1736930175000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Endothelial dysfunction in acute ischemic stroke: a review"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3009-3765","authenticated-orcid":false,"given":"Antonia","family":"Kleeberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Luft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Golkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan C.","family":"Purrucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"issue":"34","key":"12888_CR1","doi-asserted-by":"publisher","first-page":"4209","DOI":"10.2174\/1381612826666200417154126","volume":"26","author":"A Tuttolomondo","year":"2020","unstructured":"Tuttolomondo A, Daidone M, Pinto A (2020) Endothelial dysfunction and inflammation in ischemic stroke pathogenesis. Curr Pharm Des 26(34):4209\u20134219. https:\/\/doi.org\/10.2174\/1381612826666200417154126","journal-title":"Curr Pharm Des"},{"key":"12888_CR2","doi-asserted-by":"publisher","first-page":"S75","DOI":"10.1097\/00005344-200111002-00018","volume":"38","author":"F Cosentino","year":"2001","unstructured":"Cosentino F, Rubattu S, Savoia C, Venturelli V, Pagannonne E, Volpe M (2001) Endothelial dysfunction and stroke. J Cardiovasc Pharmacol 38:S75","journal-title":"J Cardiovasc Pharmacol"},{"issue":"1","key":"12888_CR3","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.neuron.2017.07.030","volume":"96","author":"C Iadecola","year":"2017","unstructured":"Iadecola C (2017) The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron 96(1):17\u201342. https:\/\/doi.org\/10.1016\/j.neuron.2017.07.030","journal-title":"Neuron"},{"issue":"13_Supplement_1","key":"12888_CR4","doi-asserted-by":"publisher","first-page":"S58","DOI":"10.1212\/WNL.0b013e3182695836","volume":"79","author":"JA Madden","year":"2012","unstructured":"Madden JA (2012) Role of the vascular endothelium and plaque in acute ischemic stroke. Neurology 79(13_Supplement_1):S58\u2013S62. https:\/\/doi.org\/10.1212\/WNL.0b013e3182695836","journal-title":"Neurology"},{"issue":"2","key":"12888_CR5","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1161\/01.RES.0000255691.76142.4a","volume":"100","author":"WC Aird","year":"2007","unstructured":"Aird WC (2007) Phenotypic heterogeneity of the endothelium. Circ Res 100(2):158\u2013173. https:\/\/doi.org\/10.1161\/01.RES.0000255691.76142.4a","journal-title":"Circ Res"},{"issue":"47","key":"12888_CR6","doi-asserted-by":"publisher","first-page":"23618","DOI":"10.1073\/pnas.1912409116","volume":"116","author":"ACA Cleuren","year":"2019","unstructured":"Cleuren ACA, van der Ent MA, Jiang H et al (2019) The in vivo endothelial cell translatome is highly heterogeneous across vascular beds. Proc Natl Acad Sci 116(47):23618\u201323624. https:\/\/doi.org\/10.1073\/pnas.1912409116","journal-title":"Proc Natl Acad Sci"},{"key":"12888_CR7","doi-asserted-by":"publisher","first-page":"10160","DOI":"10.1038\/ncomms10160","volume":"7","author":"L Yuan","year":"2016","unstructured":"Yuan L, Chan GC, Beeler D et al (2016) A role of stochastic phenotype switching in generating mosaic endothelial cell heterogeneity. Nat Commun 7:10160. https:\/\/doi.org\/10.1038\/ncomms10160","journal-title":"Nat Commun"},{"issue":"5","key":"12888_CR8","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/jemt.10088","volume":"57","author":"M Bendayan","year":"2002","unstructured":"Bendayan M (2002) Morphological and cytochemical aspects of capillary permeability. Microsc Res Tech 57(5):327\u2013349. https:\/\/doi.org\/10.1002\/jemt.10088","journal-title":"Microsc Res Tech"},{"issue":"5","key":"12888_CR9","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/jemt.10086","volume":"57","author":"M Simionescu","year":"2002","unstructured":"Simionescu M, Gafencu A, Antohe F (2002) Transcytosis of plasma macromolecules in endothelial cells: a cell biological survey. Microsc Res Tech 57(5):269\u2013288. https:\/\/doi.org\/10.1002\/jemt.10086","journal-title":"Microsc Res Tech"},{"issue":"1","key":"12888_CR10","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/jcbfm.2015.116","volume":"36","author":"A Poggesi","year":"2016","unstructured":"Poggesi A, Pasi M, Pescini F, Pantoni L, Inzitari D (2016) Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: a review. J Cereb Blood Flow Metab 36(1):72\u201394. https:\/\/doi.org\/10.1038\/jcbfm.2015.116","journal-title":"J Cereb Blood Flow Metab"},{"issue":"448","key":"12888_CR11","doi-asserted-by":"publisher","first-page":"eaam9507","DOI":"10.1126\/scitranslmed.aam9507","volume":"10","author":"RM Rajani","year":"2018","unstructured":"Rajani RM, Quick S, Ruigrok SR et al (2018) Reversal of endothelial dysfunction reduces white matter vulnerability in cerebral small vessel disease in rats. Sci Transl Med 10(448):eaam9507. https:\/\/doi.org\/10.1126\/scitranslmed.aam9507","journal-title":"Sci Transl Med"},{"issue":"8","key":"12888_CR12","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.651","volume":"5","author":"X Wang","year":"2024","unstructured":"Wang X, He B (2024) Endothelial dysfunction: molecular mechanisms and clinical implications. MedComm 5(8):e651. https:\/\/doi.org\/10.1002\/mco2.651","journal-title":"MedComm"},{"issue":"7","key":"12888_CR13","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1016\/S1474-4422(19)30079-1","volume":"18","author":"JM Wardlaw","year":"2019","unstructured":"Wardlaw JM, Smith C, Dichgans M (2019) Small vessel disease: mechanisms and clinical implications. Lancet Neurol 18(7):684\u2013696. https:\/\/doi.org\/10.1016\/S1474-4422(19)30079-1","journal-title":"Lancet Neurol"},{"issue":"10","key":"12888_CR14","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1001\/jamaneurol.2018.1073","volume":"75","author":"RW Regenhardt","year":"2018","unstructured":"Regenhardt RW, Das AS, Lo EH, Caplan LR (2018) Advances in lacunar stroke pathophysiology: a review. JAMA Neurol 75(10):1273\u20131281. https:\/\/doi.org\/10.1001\/jamaneurol.2018.1073","journal-title":"JAMA Neurol"},{"key":"12888_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70060-7","author":"J Wardlaw","year":"2013","unstructured":"Wardlaw J, Smith C, Dichgans M (2013) Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol. https:\/\/doi.org\/10.1016\/S1474-4422(13)70060-7","journal-title":"Lancet Neurol"},{"issue":"4","key":"12888_CR16","doi-asserted-by":"publisher","first-page":"H2009","DOI":"10.1152\/ajpheart.00522.2007","volume":"293","author":"SA Cooper","year":"2007","unstructured":"Cooper SA, Whaley-Connell A, Habibi J et al (2007) Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance. Am J Physiol-Heart Circ Physiol 293(4):H2009\u2013H2023. https:\/\/doi.org\/10.1152\/ajpheart.00522.2007","journal-title":"Am J Physiol-Heart Circ Physiol"},{"key":"12888_CR17","unstructured":"Kleeberg A (2024) Created in BioRender. BioRender.com\/i60x318"},{"issue":"10","key":"12888_CR18","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.7150\/ijbs.7502","volume":"9","author":"P Rajendran","year":"2013","unstructured":"Rajendran P, Rengarajan T, Thangavel J et al (2013) The vascular endothelium and human diseases. Int J Biol Sci 9(10):1057\u20131069. https:\/\/doi.org\/10.7150\/ijbs.7502","journal-title":"Int J Biol Sci"},{"key":"12888_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2013.05.047","volume":"1524","author":"C Pieper","year":"2013","unstructured":"Pieper C, Pieloch P, Galla HJ (2013) Pericytes support neutrophil transmigration via interleukin-8 across a porcine co-culture model of the blood-brain barrier. Brain Res 1524:1\u201311. https:\/\/doi.org\/10.1016\/j.brainres.2013.05.047","journal-title":"Brain Res"},{"issue":"2","key":"12888_CR20","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1093\/cvr\/cvv107","volume":"106","author":"MC Durp\u00e8s","year":"2015","unstructured":"Durp\u00e8s MC, Morin C, Paquin-Veillet J et al (2015) PKC-\u03b2 activation inhibits IL-18-binding protein causing endothelial dysfunction and diabetic atherosclerosis. Cardiovasc Res 106(2):303\u2013313. https:\/\/doi.org\/10.1093\/cvr\/cvv107","journal-title":"Cardiovasc Res"},{"key":"12888_CR21","doi-asserted-by":"publisher","unstructured":"Bach LA (2015) Endothelial cells and the IGF system. https:\/\/doi.org\/10.1530\/JME-14-0215","DOI":"10.1530\/JME-14-0215"},{"issue":"1","key":"12888_CR22","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1159\/000356789","volume":"37","author":"S Wiseman","year":"2013","unstructured":"Wiseman S, Marlborough F, Doubal F, Webb DJ, Wardlaw J (2013) Blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-lacunar stroke and non-stroke: systematic review and meta-analysis. Cerebrovasc Dis 37(1):64\u201375. https:\/\/doi.org\/10.1159\/000356789","journal-title":"Cerebrovasc Dis"},{"issue":"4","key":"12888_CR23","doi-asserted-by":"publisher","first-page":"867","DOI":"10.3390\/ijms20040867","volume":"20","author":"R Esse","year":"2019","unstructured":"Esse R, Barroso M, Tavares de Almeida I, Castro R (2019) The contribution of homocysteine metabolism disruption to endothelial dysfunction: state-of-the-art. Int J Mol Sci 20(4):867. https:\/\/doi.org\/10.3390\/ijms20040867","journal-title":"Int J Mol Sci"},{"issue":"3\u20134","key":"12888_CR24","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1080\/1354750X.2017.1286689","volume":"22","author":"B Piccardi","year":"2017","unstructured":"Piccardi B, Giralt D, Bustamante A et al (2017) Blood markers of inflammation and endothelial dysfunction in cardioembolic stroke: systematic review and meta-analysis. Biomark Biochem Indic Expo Response Susceptibility Chem 22(3\u20134):200\u2013209. https:\/\/doi.org\/10.1080\/1354750X.2017.1286689","journal-title":"Biomark Biochem Indic Expo Response Susceptibility Chem"},{"issue":"4","key":"12888_CR25","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1002\/joa3.12077","volume":"34","author":"P Korantzopoulos","year":"2018","unstructured":"Korantzopoulos P, Letsas KP, Tse G, Fragakis N, Goudis CA, Liu T (2018) Inflammation and atrial fibrillation: a comprehensive review. J Arrhythmia 34(4):394\u2013401. https:\/\/doi.org\/10.1002\/joa3.12077","journal-title":"J Arrhythmia"},{"issue":"10","key":"12888_CR26","doi-asserted-by":"publisher","first-page":"2550","DOI":"10.3390\/biomedicines10102550","volume":"10","author":"M Marcic","year":"2022","unstructured":"Marcic M, Marcic L, Lovric Kojundzic S, Marinovic Guic M, Marcic B, Caljkusic K (2022) Chronic endothelial dysfunction after COVID-19 infection shown by transcranial color-coded doppler: a cross-sectional study. Biomedicines 10(10):2550. https:\/\/doi.org\/10.3390\/biomedicines10102550","journal-title":"Biomedicines"},{"key":"12888_CR27","first-page":"283","volume":"19","author":"A Suessenbacher","year":"2012","unstructured":"Suessenbacher A, Frick M, Alber H (2012) Periphere Endothelfunktionsmessung\u2014anwendung in der t\u00e4glichen klinischen Praxis gerechtfertigt? Austrian J Cardiol 19:283\u2013288","journal-title":"Austrian J Cardiol"},{"issue":"1","key":"12888_CR28","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s10334-017-0644-x","volume":"31","author":"BF Coolen","year":"2018","unstructured":"Coolen BF, Calcagno C, van Ooij P, Fayad ZA, Strijkers GJ, Nederveen AJ (2018) Vessel wall characterization using quantitative MRI: what\u2019s in a number? Magma N Y N 31(1):201\u2013222. https:\/\/doi.org\/10.1007\/s10334-017-0644-x","journal-title":"Magma N Y N"},{"issue":"9","key":"12888_CR29","doi-asserted-by":"publisher","first-page":"e414","DOI":"10.1016\/S2352-3026(17)30108-4","volume":"4","author":"T Luft","year":"2017","unstructured":"Luft T, Benner A, Jodele S et al (2017) EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis. Lancet Haematol 4(9):e414\u2013e423. https:\/\/doi.org\/10.1016\/S2352-3026(17)30108-4","journal-title":"Lancet Haematol"},{"issue":"3","key":"12888_CR30","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.blre.2014.11.001","volume":"29","author":"S Jodele","year":"2015","unstructured":"Jodele S, Laskin BL, Dandoy CE et al (2015) A new paradigm: diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury. Blood Rev 29(3):191\u2013204. https:\/\/doi.org\/10.1016\/j.blre.2014.11.001","journal-title":"Blood Rev"},{"issue":"9","key":"12888_CR31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075984","volume":"8","author":"G Parra-Bonilla","year":"2013","unstructured":"Parra-Bonilla G, Alvarez DF, Alexeyev M, Vasauskas A, Stevens T (2013) Lactate dehydrogenase a expression is necessary to sustain rapid angiogenesis of pulmonary microvascular endothelium. PLoS ONE 8(9):e75984. https:\/\/doi.org\/10.1371\/journal.pone.0075984","journal-title":"PLoS ONE"},{"issue":"13","key":"12888_CR32","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1161\/hc3801.095588","volume":"104","author":"AD Michelson","year":"2001","unstructured":"Michelson AD, Barnard MR, Krueger LA, Valeri CR, Furman MI (2001) Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin. Circulation 104(13):1533\u20131537. https:\/\/doi.org\/10.1161\/hc3801.095588","journal-title":"Circulation"},{"issue":"3","key":"12888_CR33","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/s41409-019-0703-1","volume":"55","author":"T Luft","year":"2020","unstructured":"Luft T, Benner A, Terzer T et al (2020) EASIX and mortality after allogeneic stem cell transplantation. Bone Marrow Transplant 55(3):553\u2013561. https:\/\/doi.org\/10.1038\/s41409-019-0703-1","journal-title":"Bone Marrow Transplant"},{"issue":"11","key":"12888_CR34","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41408-019-0247-z","volume":"9","author":"A Merz","year":"2019","unstructured":"Merz A, Germing U, Kobbe G et al (2019) EASIX for prediction of survival in lower-risk myelodysplastic syndromes. Blood Cancer J 9(11):85. https:\/\/doi.org\/10.1038\/s41408-019-0247-z","journal-title":"Blood Cancer J"},{"key":"12888_CR35","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-024-02534-y","author":"D Finke","year":"2024","unstructured":"Finke D, Hund H, Frey N, Luft T, Lehmann LH (2024) EASIX (endothelial activation and stress index) predicts mortality in patients with coronary artery disease. Clin Res Cardiol. https:\/\/doi.org\/10.1007\/s00392-024-02534-y","journal-title":"Clin Res Cardiol"},{"issue":"2","key":"12888_CR36","doi-asserted-by":"publisher","DOI":"10.1111\/eci.13883","volume":"53","author":"C Pabst","year":"2023","unstructured":"Pabst C, Schreck N, Benner A et al (2023) Statin-based endothelial prophylaxis and outcome after allogeneic stem cell transplantation. Eur J Clin Invest 53(2):e13883. https:\/\/doi.org\/10.1111\/eci.13883","journal-title":"Eur J Clin Invest"},{"issue":"2","key":"12888_CR37","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1136\/jnnp.2008.153460","volume":"80","author":"FN Doubal","year":"2009","unstructured":"Doubal FN, Hokke PE, Wardlaw JM (2009) Retinal microvascular abnormalities and stroke: a systematic review. J Neurol Neurosurg Psychiatry 80(2):158\u2013165. https:\/\/doi.org\/10.1136\/jnnp.2008.153460","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"4","key":"12888_CR38","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1097\/HJH.0000000000003071","volume":"40","author":"J Li","year":"2022","unstructured":"Li J, Imano H, Kitamura A et al (2022) Retinal microvascular abnormalities and risks of incident stroke and its subtypes: the circulatory risk in communities study. J Hypertens 40(4):732\u2013740. https:\/\/doi.org\/10.1097\/HJH.0000000000003071","journal-title":"J Hypertens"},{"issue":"4","key":"12888_CR39","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1159\/000117444","volume":"37","author":"A Arboix","year":"1997","unstructured":"Arboix A, Besses C (1997) Cerebrovascular disease as the initial clinical presentation of haematological disorders. Eur Neurol 37(4):207\u2013211. https:\/\/doi.org\/10.1159\/000117444","journal-title":"Eur Neurol"},{"issue":"1","key":"12888_CR40","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/1471-2377-10-31","volume":"10","author":"A Arboix","year":"2010","unstructured":"Arboix A, Massons J, Garc\u00eda-Eroles L, Targa C, Comes E, Parra O (2010) Clinical predictors of lacunar syndrome not due to lacunar infarction. BMC Neurol 10(1):31. https:\/\/doi.org\/10.1186\/1471-2377-10-31","journal-title":"BMC Neurol"},{"issue":"10","key":"12888_CR41","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.1161\/STROKEAHA.110.586289","volume":"41","author":"RG Wieberdink","year":"2010","unstructured":"Wieberdink RG, van Schie MC, Koudstaal PJ et al (2010) High von Willebrand factor levels increase the risk of stroke: the Rotterdam study. Stroke 41(10):2151\u20132156. https:\/\/doi.org\/10.1161\/STROKEAHA.110.586289","journal-title":"Stroke"},{"key":"12888_CR42","doi-asserted-by":"publisher","DOI":"10.1159\/000530372","author":"X Zhang","year":"2023","unstructured":"Zhang X, Gong P, Chen S et al (2023) Endothelial dysfunction and parenchymal hematoma in ischemic stroke patients after endovascular thrombectomy. Cerebrovasc Dis. https:\/\/doi.org\/10.1159\/000530372","journal-title":"Cerebrovasc Dis"},{"issue":"Suppl","key":"12888_CR43","first-page":"86","volume":"57","author":"S Ch\u0142opicki","year":"2005","unstructured":"Ch\u0142opicki S, Gryglewski RJ (2005) Angiotensin converting enzyme (ACE) and HydroxyMethylGlutaryl-CoA (HMG-CoA) reductase inhibitors in the forefront of pharmacology of endothelium. Pharmacol Rep PR 57(Suppl):86\u201396","journal-title":"Pharmacol Rep PR"},{"issue":"4","key":"12888_CR44","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1161\/01.STR.32.4.980","volume":"32","author":"S Amin-Hanjani","year":"2001","unstructured":"Amin-Hanjani S, Stagliano NE, Yamada M, Huang PL, Liao JK, Moskowitz MA (2001) Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice. Stroke 32(4):980\u2013986. https:\/\/doi.org\/10.1161\/01.STR.32.4.980","journal-title":"Stroke"},{"issue":"10","key":"12888_CR45","doi-asserted-by":"publisher","first-page":"2640","DOI":"10.1161\/01.STR.0000240690.69406.28","volume":"37","author":"M Endres","year":"2006","unstructured":"Endres M, Laufs U (2006) Discontinuation of statin treatment in stroke patients. Stroke 37(10):2640\u20132643. https:\/\/doi.org\/10.1161\/01.STR.0000240690.69406.28","journal-title":"Stroke"},{"issue":"3","key":"12888_CR46","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1056\/NEJM200001203420301","volume":"342","author":"The Heart Outcomes Prevention Evaluation Study Investigators","year":"2000","unstructured":"The Heart Outcomes Prevention Evaluation Study Investigators (2000) Effects of an angiotensin-converting\u2013enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 342(3):145\u2013153. https:\/\/doi.org\/10.1056\/NEJM200001203420301","journal-title":"N Engl J Med"},{"issue":"10","key":"12888_CR47","doi-asserted-by":"publisher","first-page":"707","DOI":"10.3109\/00207454.2013.872102","volume":"124","author":"J Kurzepa","year":"2014","unstructured":"Kurzepa J, Kurzepa J, Golab P, Czerska S, Bielewicz J (2014) The significance of matrix metalloproteinase (MMP)-2 and MMP-9 in the ischemic stroke. Int J Neurosci 124(10):707\u2013716. https:\/\/doi.org\/10.3109\/00207454.2013.872102","journal-title":"Int J Neurosci"},{"key":"12888_CR48","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.neuroscience.2016.09.036","volume":"339","author":"A Watanabe","year":"2016","unstructured":"Watanabe A, Sasaki T, Yukami T et al (2016) Serine racemase inhibition induces nitric oxide-mediated neurovascular protection during cerebral ischemia. Neuroscience 339:139\u2013149. https:\/\/doi.org\/10.1016\/j.neuroscience.2016.09.036","journal-title":"Neuroscience"},{"issue":"4","key":"12888_CR49","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1248\/bpb.31.633","volume":"31","author":"Q Hua","year":"2008","unstructured":"Hua Q, Zhu X, Li P et al (2008) Refined Qing Kai Ling, traditional Chinese medicinal preparation, reduces ischemic stroke-induced infarct size and neurological deficits and increases expression of endothelial nitric oxide synthase. Biol Pharm Bull 31(4):633\u2013637. https:\/\/doi.org\/10.1248\/bpb.31.633","journal-title":"Biol Pharm Bull"},{"issue":"7","key":"12888_CR50","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1001\/jamaneurol.2023.1526","volume":"80","author":"JM Wardlaw","year":"2023","unstructured":"Wardlaw JM, Woodhouse LJ, Mhlanga II et al (2023) Isosorbide mononitrate and cilostazol treatment in patients with symptomatic cerebral small vessel disease: the lacunar intervention trial-2 (LACI-2) randomized clinical trial. JAMA Neurol 80(7):682\u2013692. https:\/\/doi.org\/10.1001\/jamaneurol.2023.1526","journal-title":"JAMA Neurol"},{"issue":"1","key":"12888_CR51","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s12883-017-0950-y","volume":"17","author":"SJ Lee","year":"2017","unstructured":"Lee SJ, Lee JS, Choi MH, Lee SE, Shin DH, Hong JM (2017) Cilostazol improves endothelial function in acute cerebral ischemia patients: a double-blind placebo controlled trial with flow-mediated dilation technique. BMC Neurol 17(1):169. https:\/\/doi.org\/10.1186\/s12883-017-0950-y","journal-title":"BMC Neurol"},{"key":"12888_CR52","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.jad.2022.08.007","volume":"316","author":"D Delialis","year":"2022","unstructured":"Delialis D, Mavraganis G, Dimoula A et al (2022) A systematic review and meta-analysis on the effect of selective serotonin reuptake inhibitors on endothelial function. J Affect Disord 316:71\u201375. https:\/\/doi.org\/10.1016\/j.jad.2022.08.007","journal-title":"J Affect Disord"},{"issue":"9","key":"12888_CR53","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.156","volume":"6","author":"I Lopez-Vilchez","year":"2016","unstructured":"Lopez-Vilchez I, Diaz-Ricart M, Navarro V et al (2016) Endothelial damage in major depression patients is modulated by SSRI treatment, as demonstrated by circulating biomarkers and an in vitro cell model. Transl Psychiatry 6(9):e886. https:\/\/doi.org\/10.1038\/tp.2016.156","journal-title":"Transl Psychiatry"},{"issue":"8","key":"12888_CR54","doi-asserted-by":"publisher","first-page":"R814","DOI":"10.1152\/ajpregu.00337.2014","volume":"309","author":"VV Matchkov","year":"2015","unstructured":"Matchkov VV, Kravtsova VV, Wiborg O, Aalkjaer C, Bouzinova EV (2015) Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression. Am J Physiol Regul Integr Comp Physiol 309(8):R814\u2013R823. https:\/\/doi.org\/10.1152\/ajpregu.00337.2014","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"6","key":"12888_CR55","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1159\/000524414","volume":"51","author":"L Lu","year":"2022","unstructured":"Lu L, Zhu J, Zhang H, Li X, Chen K (2022) Advances in the pharmacological intervention of endothelial progenitor cells in the treatment of ischemic stroke. Cerebrovasc Dis 51(6):697\u2013705. https:\/\/doi.org\/10.1159\/000524414","journal-title":"Cerebrovasc Dis"},{"issue":"1","key":"12888_CR56","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1002\/sctm.18-0012","volume":"8","author":"J Fang","year":"2019","unstructured":"Fang J, Guo Y, Tan S et al (2019) Autologous endothelial progenitor cells transplantation for acute ischemic stroke: a 4-year follow-up study. Stem Cells Transl Med 8(1):14\u201321. https:\/\/doi.org\/10.1002\/sctm.18-0012","journal-title":"Stem Cells Transl Med"},{"issue":"4","key":"12888_CR57","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1007\/s13346-017-0464-6","volume":"8","author":"RY Kiseleva","year":"2018","unstructured":"Kiseleva RY, Glassman PM, Greineder CF, Hood ED, Shuvaev VV, Muzykantov VR (2018) Targeting therapeutics to endothelium: are we there yet? Drug Deliv Transl Res 8(4):883\u2013902. https:\/\/doi.org\/10.1007\/s13346-017-0464-6","journal-title":"Drug Deliv Transl Res"},{"key":"12888_CR58","doi-asserted-by":"publisher","first-page":"3846","DOI":"10.1038\/s41598-017-03309-4","volume":"7","author":"EM Lutton","year":"2017","unstructured":"Lutton EM, Razmpour R, Andrews AM et al (2017) Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury. Sci Rep 7:3846. https:\/\/doi.org\/10.1038\/s41598-017-03309-4","journal-title":"Sci Rep"},{"key":"12888_CR59","unstructured":"Kleeberg A (2024) Created in BioRender. BioRender.com\/p12y720"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-025-12888-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-025-12888-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-025-12888-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T11:40:11Z","timestamp":1739619611000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-025-12888-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,15]]},"references-count":59,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["12888"],"URL":"https:\/\/doi.org\/10.1007\/s00415-025-12888-6","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,15]]},"assertion":[{"value":"6 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 December 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no competing interests to declare that are relevant to the content of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}],"article-number":"143"}}