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The role of endothelial dysfunction and oxidative stress in cerebrovascular diseases

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Pages 579-595 | Received 08 Feb 2019, Accepted 13 May 2019, Published online: 04 Jun 2019

References

  • Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics – 2013 update: a report from the American Heart Association. Circulation. 2013;127(1):e6–e245.
  • Hankey GJ. Stroke in young adults: implications of the long-term prognosis. JAMA. 2013;309(11):1171–1172.
  • Roach ES, Golomb MR, Adams R, et al. Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke. 2008;39(9):2644–2691.
  • Mohr JP, Albers GW, Amarenco P, et al. American Heart Association Prevention Conference. IV. Prevention and Rehabilitation of Stroke. Etiology of stroke. Stroke. 1997;28(7):1501–1506.
  • Chandra A, Li WA, Stone CR, et al. The cerebral circulation and cerebrovascular disease I: anatomy. Brain Circ. 2017;3(2):45–56.
  • Chandra A, Stone CR, Li WA, et al. The cerebral circulation and cerebrovascular disease II: pathogenesis of cerebrovascular disease. Brain Circ. 2017;3(2):57–65.
  • Chandra A, Stone CR, Du X, et al. The cerebral circulation and cerebrovascular disease III: stroke. Brain Circ. 2017;3(2):66–77.
  • Ciccone MM, Miniello V, Marchioli R, et al. Morphological and functional vascular changes induced by childhood obesity. Eur J Cardiovasc Prev Rehabil. 2011;18(6):831–835.
  • Ciccone MM, Scicchitano P, Salerno C, et al. Aorta structural alterations in term neonates: the role of birth and maternal characteristics. BioMed Res Int. 2013;2013:459168.
  • Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med. 1999;340(2):115–126.
  • Ciccone MM, Cortese F, Gesualdo M, et al. Dietary intake of carotenoids and their antioxidant and anti-inflammatory effects in cardiovascular care. Mediators Inflamm. 2013;2013:782137.
  • Sumpio BE, Riley JT, Dardik A. Cells in focus: endothelial cell. Int J Biochem Cell Biol. 2002;34(12):1508–1512.
  • Brunner H, Cockcroft JR, Deanfield J, et al. Endothelial function and dysfunction. Part II: association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005;23(2):233–246.
  • Cosentino F, Rubattu S, Savoia C, et al. Endothelial dysfunction and stroke. J Cardiovasc Pharmacol. 2001;38:S75–S78.
  • Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation. 2005;111(3):363–368.
  • Rundek T, Hundle R, Ratchford E, et al. Endothelial dysfunction is associated with carotid plaque: a cross-sectional study from the population based Northern Manhattan Study. BMC Cardiovasc Disord. 2006;6:35.
  • Fichtlscherer S, Breuer S, Zeiher AM. Prognostic value of systemic endothelial dysfunction in patients with acute coronary syndromes: further evidence for the existence of the ‘vulnerable’ patient. Circulation. 2004;110(14):1926–1932.
  • Santos-García D, Blanco M, Serena J, et al. Impaired brachial flow-mediated dilation is a predictor of a new-onset vascular event after stroke. Cerebrovasc Dis. 2011;32(2):155–162.
  • Müller M, Voges M, Piepgras U, et al. Assessment of cerebral vasomotor reactivity by transcranial Doppler ultrasound and breath-holding. A comparison with acetazolamide as vasodilatory stimulus. Stroke. 1995;26(1):96–100.
  • Haussen DC, Katsnelson M, Rodriguez A, et al. Moderate correlation between breath-holding and CO(2) Inhalation/hyperventilation methods for transcranial Doppler evaluation of cerebral vasoreactivity. J Clin Ultrasound. 2012;40(9):554–558.
  • Portegies ML, de Bruijn RF, Hofman A, et al. Cerebral vasomotor reactivity and risk of mortality: the Rotterdam Study. Stroke. 2014;45(1):42–47.
  • Ju K, Zhong L, Ni X, et al. Cerebral vasomotor reactivity predicts the development of acute stroke in patients with internal carotid artery stenosis. Neurol Neurochir Pol. 2018;52(3):374–378.
  • Staszewski J, Skrobowska E, Piusińska-Macoch R, et al. Cerebral and extracerebral vasoreactivity in patients with different clinical manifestations of cerebral small-vessel disease: data from the significance of hemodynamic and hemostatic factors in the course of different manifestations of cerebral small-vessel disease study. J Ultrasound Med. 2019;38(4):975–987.
  • Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9(7):689–701.
  • Fu JH, Lu CZ, Hong Z, et al. Relationship between cerebral vasomotor reactivity and white matter lesions in elderly subjects without large artery occlusive disease. J Neuroimaging. 2006;16(2):120–125.
  • Faraci FM, Heistad DD. Regulation of the cerebral circulation: role of endothelium and potassium channels. Physiol Rev. 1998;78(1):53–97.
  • Abbott NJ, Rönnbäck L, Hansson E. Astrocyte-endothelial interactions at the blood–brain barrier. Nat Rev Neurosci. 2006;7(1):41–53.
  • Miyamoto N, Pham LD, Seo JH, et al. Crosstalk between cerebral endothelium and oligodendrocyte. Cell Mol Life Sci. 2014;71(6):1055–1066.
  • Hassan A, Hunt BJ, O’Sullivan M, et al. Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis. Brain. 2003;126(2):424–432.
  • Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007;115(10):1285–1295.
  • Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336(15):1066–1071.
  • Tsihlis ND, Oustwani CS, Vavra AK, et al. Nitric oxide inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia by increasing the ubiquitination and degradation of UbcH10. Cell Biochem Biophys. 2011;60(1–2):89–97.
  • Stone KP, Kastin AJ, Pan W. NFκB is an unexpected major mediator of interleukin-15 signaling in cerebral endothelia. Cell Physiol Biochem. 2011;28(1):115–124.
  • Himadri P, Kumari SS, Chitharanjan M, et al. Role of oxidative stress and inflammation in hypoxia-induced cerebral edema: a molecular approach. High Alt Med Biol. 2010;11(3):231–244.
  • Wenzel P, Kossmann S, Münzel T, et al. Redox regulation of cardiovascular inflammation – immunomodulatory function of mitochondrial and Nox-derived reactive oxygen and nitrogen species. Free Radic Biol Med. 2017;109:48–60.
  • Bustamante A, Simats A, Vilar-Bergua A, et al. Blood/brain biomarkers of inflammation after stroke and their association with outcome: from C-reactive protein to damage-associated molecular patterns. Neurotherapeutics. 2016;13(4):671–684.
  • Li SJ, Zhang YF, Ma SH, et al. The role of NLRP3 inflammasome in stroke and central poststroke pain. Med Baltimore. 2018;97(33):e11861.
  • Ismael S, Zhao L, Nasoohi S, et al. Inhibition of the NLRP3-inflammasome as a potential approach for neuroprotection after stroke. Sci Rep. 2018;8(1):5971.
  • Gong Z, Pan J, Shen Q, et al. Mitochondrial dysfunction induces NLRP3 inflammasome activation during cerebral ischemia/reperfusion injury. J Neuroinflamm. 2018;15(1):242.
  • Shimada K, Crother TR, Karlin J, et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity. 2012;36(3):401–414.
  • Yamasaki K, Muto J, Taylor KR, et al. NLRP3/cryopyrin is necessaryfor interleukin-1beta (IL-1beta) release in response to hyaluronan, anendogenous trigger of inflammation in response to injury. J Biol Chem. 2009;284(19):12762–12771.
  • Shi X, Xie WL, Kong WW, et al. Expression of the NLRP3 inflammasome in carotid atherosclerosis. J Stroke Cerebrovasc Dis. 2015;24(11):2455–2466.
  • Huang JM, Hu J, Chen N, et al. Relationship between plasma high-mobility group box-1 levels and clinical outcomes of ischemicstroke. J Crit Care. 2013;28(5):792–797.
  • Sapojnikova N, Kartvelishvili T, Asatiani N, et al. Correlation betweenMMP-9 and extracellular cytokine HMGB1 in predictionof human ischemic stroke outcome. Biochim Biophys Acta. 2014;1842(9):1379–1384.
  • Sokół B, Woźniak A, Jankowski R, et al. HMGB1 level in cerebrospinal fluid as a marker of treatment outcome in patients withacute hydrocephalus following aneurysmal subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 2015;24(8):1897–1904.
  • Mattson MP. Neuroprotective signal transduction: relevance to stroke. Neurosci Biobehav Rev. 1997;21(2):193–206.
  • Wakkach A, Cottrez F, Groux H. Can interleukin-10 be used as a true immunoregulatory cytokine? Eur Cytokine Netw. 2000;11(2):153–160.
  • Caligiuri G, Rudling M, Ollivier V, et al. Interleukin-10 deficiency increases atherosclerosis, thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice. Mol Med. 2003;9(1–2):10–17.
  • Cruz Y, García EE, Gálvez JV, et al. Release of interleukin-10 and neurotrophic factors in the choroid plexus: possible inductors of neurogenesis following copolymer-1 immunization after cerebral ischemia. Neural Regen Res. 2018;13(10):1743–1752.
  • He W, Song H, Ding L, et al. Association between IL-10 gene polymorphisms and the risk of ischemic stroke in a Chinese population. Int J Clin Exp Pathol. 2015;8:13489–13494.
  • Lagerstedt L, Egea-Guerrero JJ, Rodríguez-Rodríguez A, et al. Early measurement of interleukin-10 predicts the absence of CT scan lesions in mild traumatic brain injury. PLoS One. 2018;13(2):e0193278.
  • Tian Y, Sommerville LJ, Cuneo A, et al. Expression and suppressive effects of interleukin-19 on vascular smooth muscle cell pathophysiology and development of intimal hyperplasia. Am J Pathol. 2008;173(3):901–909.
  • Gabunia K, Ellison SP, Singh H, et al. Interleukin-19 (IL-19) induces heme oxygenase-1 (HO − 1) expression and decreases reactive oxygen species in human vascular smooth muscle cells. J Biol Chem. 2012;287(4):2477–2484.
  • Gisterå A, Robertson AL, Andersson J, et al. Transforming growth factor–β signaling in T cells promotes stabilization of atherosclerotic plaques through an interleukin-17–dependent pathway. Sci Transl Med. 2013;5(196):196ra100.
  • Kim JS, Yoon SS, Kim YH, et al. Serial measurement of interleukin-6, transforming growth factor-beta, and S-100 protein in patients with acute stroke. Stroke. 1996;27(9):1553–1557.
  • Cipollone F, Fazia M, Mincione G, et al. Increased expression of transforming growth factor-beta1 as a stabilizing factor in human atherosclerotic plaques. Stroke. 2004;35(10):2253–2257.
  • Gojova A, Brun V, Esposito B, et al. Specific abrogation of transforming growth factor-beta signaling in T cells alters atherosclerotic lesion size and composition in mice. Blood. 2003;102(12):4052–4058.
  • Dollery CM, McEwan JR, Henney AM. Matrix metalloproteinases and cardiovascular disease. Circ Res. 1995;77(5):863–868.
  • Shah PK, Falk E, Badimon JJ, et al. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation. 1995;92(6):1565–1569.
  • Miller AM, Xu D, Asquith DL, et al. IL-33 reduces the development of atherosclerosis. J Exp Med. 2008;205(2):339–346.
  • Zhang SR, Piepke M, Chu HX, et al. IL-33 modulates inflammatory brain injury but exacerbates systemic immunosuppression following ischemic stroke. JCI Insight. 2018;3(18). [pii: 121560]
  • Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell. 2012;48(2):158–167.
  • Harrison R. Structure and function of xanthine oxidoreductase: where are we now? Free Radic Biol Med. 2002;33(6):774–797.
  • Nomura J, Busso N, Ives A, et al. Xanthine oxidase inhibition by febuxostat attenuates experimental atherosclerosis in mice. Sci Rep. 2014;4:4554.
  • Schröder K, Vecchione C, Jung O, et al. Xanthine oxidase inhibitor tungsten prevents the development of atherosclerosis in ApoE knockout mice fed a Western-type diet. Free Radic Biol Med. 2006;41(9):1353–1360.
  • Kigawa Y, Miyazaki T, Lei XF, et al. Functional heterogeneity of nadph oxidases in atherosclerotic and aneurysmal diseases. J Atheroscler Thromb. 2017;24(1):1–13.
  • Shami A, Gonçalves I, Hultgårdh-Nilsson A. Collagen and related extracellular matrix proteins in atheroscleroticplaque development. Curr Opin Lipidol. 2014;25(5):394–399.
  • Matés JM, Pérez-Gómez C, Núñez de Castro I. Antioxidant enzymes and human diseases. Clin Biochem. 1999;32(8):595–603.
  • McCall MR, Frei B. Can antioxidant vitamins materially reduce oxidative damage in humans? Free Radic Biol Med. 1999;26(7–8):1034–1053.
  • Fukai T, Galis ZS, Meng XP, et al. Vascular expression of extracellular superoxide dismutase in atherosclerosis. J Clin Invest. 1998;101(10):2101–2111.
  • Fukai T, Siegfried MR, Ushio-Fukai M, et al. Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension. Circ Res. 1999;85(1):23–28.
  • Gongora MC, Qin Z, Laude K, et al. Role of extracellular superoxide dismutase in hypertension. Hypertension. 2006;48(3):473–481.
  • Didion SP, Ryan MJ, Baumbach GL, et al. Superoxide contributes to vascular dysfunction in mice that express human renin and angiotensinogen. Am J Physiol Heart Circ Physiol. 2002;283(4):H1569–H1576.
  • Iida S, Chu Y, Weiss RM, et al. Vascular effects of a common gene variant of extracellular superoxide dismutase in heart failure. Am J Physiol Heart Circ Physiol. 2006;291(2):H914–H920.
  • Jung O, Marklund SL, Geiger H, et al. Extracellular superoxide dismutase is a major determinant of nitric oxide bioavailability: in vivo and ex vivo evidence from ecSOD-deficient mice. Circ Res. 2003;93(7):622–629.
  • Jung O, Marklund SL, Xia N, et al. Inactivation of extracellular superoxide dismutase contributes to the development of high-volume hypertension. Arterioscler Thromb Vasc Biol. 2007;27(3):470–477.
  • Qin Z, Reszka KJ, Fukai T, et al. Extracellular superoxide dismutase (ecSOD) in vascular biology: an update on exogenous gene transfer and endogenous regulators of ecSOD. Transl Res. 2008;151(2):68–78.
  • Oppermann M, Balz V, Adams V, et al. Pharmacological induction of vascular extracellular superoxide dismutase expression in vivo. J Cell Mol Med. 2009;13(7):1271–1278.
  • Takapoo M, Chamseddine AH, Bhalla RC, et al. Glutathione peroxidase-deficient smooth muscle cells cause paracrine activation of normal smooth muscle cells via cyclophilin A. Vascul Pharmacol. 2011;55(5–6):143–148.
  • Lewis P, Stefanovic N, Pete J, et al. Lack of the antioxidant enzyme glutathione peroxidase-1 accelerates atherosclerosis in diabetic apolipoprotein E-deficient mice. Circulation. 2007;115(16):2178–2187.
  • Sharma A, Yuen D, Huet O, et al. Lack of glutathione peroxidase-1 facilitates a pro-inflammatory and activated vascular endothelium. Vascul Pharmacol. 2016;79:32–42.
  • Yang H, Roberts LJ, Shi MJ, et al. Retardation of atherosclerosis by overexpression of catalase or both Cu/Zn-superoxide dismutase and catalase in mice lacking apolipoprotein E. Circ Res. 2004;95(11):1075–1081.
  • Christen Y. Oxidative stress and Alzheimer disease. Am J Clin Nutr. 2000;71(2):621S–629S.
  • Sosa V, Moliné T, Somoza R, et al. Oxidative stress and cancer: an overview. Ageing Res Rev. 2013;12(1):376–390.
  • Di Lisa F, Kaludercic N, Carpi A, et al. Mitochondrial pathways for ROS formation and myocardial injury: the relevance of p66(Shc) and monoamine oxidase. Basic Res Cardiol. 2009;104(2):131–139.
  • Nanetti L, Taffi R, Vignini A, et al. Reactive oxygen species plasmatic levels in ischemic stroke. Mol Cell Biochem. 2007;303(1–2):19–25.
  • Kehrer JP. Free radicals as mediators of tissue injury and disease. Crit Rev Toxicol. 1993;23(1):21–48.
  • Victor VM, Rocha M, Solá E, et al. Oxidative stress, endothelial dysfunction and atherosclerosis. Curr Pharm Des. 2009;15(26):2988–3002.
  • Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol. 2006;6(7):508–519.
  • Nilsson J, Hansson GK. Autoimmunity in atherosclerosis: a protective response losing control? J Intern Med. 2008;263(5):464–478.
  • Frostegård J, Nilsson J, Haegerstrand A, et al. Oxidized low density lipoprotein induces differentiation and adhesion of human monocytes and the monocytic cell line U937. Proc Natl Acad Sci U S A. 1990;87(3):904–908.
  • Steinberg D., Lewis A. Conner Memorial Lecture. Oxidative modification of LDL and atherogenesis. Circulation. 1997;95(4):1062–1071.
  • Morel DW, Hessler JR, Chisolm GM. Low density lipoprotein cytotoxicity induced by free radical peroxidation of lipid. J Lipid Res. 1983;24(8):1070–1076.
  • Huang Y, Mironova M, Lopes-Virella MF. Oxidized LDL stimulates matrix metalloproteinase-1 expression in human vascular endothelial cells. Arterioscler Thromb Vasc Biol. 1999;19(11):2640–2647.
  • Liu B, Sidiropoulos A, Zhao B, et al. Oxidized LDL damages endothelial cell monolayer and promotes thrombocyte adhesion. Am J Hematol. 1998;57(4):341–343.
  • Chai YC, Binion DG, Macklis R, et al. Smooth muscle cell proliferation induced by oxidized LDL-borne lysophosphatidylcholine. Evidence for FGF-2 release from cells not extracellular matrix. Vasc Pharmacol. 2002;38:229–237.
  • Tamai O, Matsuoka H, Itabe H, et al. Single LDL apheresis improves endothelium-dependent vasodilatation in hypercholesterolemic humans. Circulation. 1997;95(1):76–82.
  • Galle J, Hansen-Hagge T, Wanner C, et al. Impact of oxidized low density lipoprotein on vascular cells. Atherosclerosis. 2006;185(2):219–226.
  • Thomas CE, Jackson RL, Ohlweiler DF, et al. Multiple lipid oxidation products in low density lipoproteins induce interleukin-1beta release from human blood mononuclear cells. J Lipid Res. 1994;35(3):417–427.
  • Mylonas C, Kouretas D. Lipid peroxidation and tissue damage. In Vivo. 1999;13(3):295–309.
  • Niki E. Lipid peroxidation: physiological levels and dual biological effects. Free Radic Biol Med. 2009;47(5):469–484.
  • Steinberg D, Parthasarathy S, Carew TE, et al. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989;320(14):915–924.
  • Stiko A, Regnström J, Shah PK, et al. Active oxygen species and lysophosphatidylcholine are involved in oxidized low density lipoprotein activation of smooth muscle cell DNA synthesis. Arterioscler Thromb Vasc Biol. 1996;16(2):194–200.
  • Allen CL, Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int J Stroke. 2009;4(6):461–470.
  • Guldiken B, Guldiken S, Turgut B, et al. The roles of oxidized low-density lipoprotein and interleukin-6 levels in acute atherothrombotic and lacunar ischemic stroke. Angiology. 2008;59(2):224–229.
  • Uno M, Harada M, Takimoto O, et al. Elevation of plasma oxidized LDL in acute stroke patients is associated with ischemic lesions depicted by DWI and predictive of infarct enlargement. Neurol Res. 2005;27(1):94–102.
  • Aygul R, Kotan D, Demirbas F, et al. Plasma oxidants and antioxidants in acute ischaemic stroke. J Int Med Res. 2006;34(4):413–418.
  • Pacher P, Nivorozhkin A, Szabó C. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev. 2006;58(1):87–114.
  • Jian Liu K, Rosenberg GA. Matrix metalloproteinases and free radicals in cerebral ischemia. Free Radic Biol Med. 2005;39(1):71–80.
  • Montaner J, Molina CA, Monasterio J, et al. Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications afterthrombolysis in human stroke. Circulation. 2003;107(4):598–603.
  • Zhang XH, Lei H, Liu AJ, et al. Increased oxidative stress is responsible for severer cerebral infarction in stroke-prone spontaneously hypertensive rats. CNS Neurosci Ther. 2011;17(6):590–598.
  • Nakajima H, Kubo T, Ihara H, et al. Nuclear-translocated glyceraldehyde-3-phosphate dehydrogenase promotes poly(ADP-ribose) polymerase-1 activation during oxidative/nitrosative stress in stroke. J Biol Chem. 2015;290(23):14493–14503.
  • McCarty MF. NADPH oxidase activity in cerebral arterioles is a key mediator of cerebral small vessel disease-implications for prevention. Healthcare. 2015;3(2):233–251.
  • Adameova A, Xu YJ, Duhamel TA, et al. Anti-atherosclerotic molecules targeting oxidative stress and inflammation. Curr Pharm Des. 2009;15(27):3094–3107.
  • Scicchitano P, Cameli M, Maiello M, et al. Nutraceuticals and dyslipidaemia: beyond the common therapeutics. J Funct Foods. 2014;6:11–32.
  • Murad LB, Guimarães MR, Paganelli A, et al. Alpha-tocopherol in the brain tissue preservation of stroke-prone spontaneously hypertensive rats. J Physiol Biochem. 2014;70(1):49–60.
  • Song J, Park J, Kim JH, et al. Dehydroascorbic acid attenuates ischemic brain edema and neurotoxicity in cerebral ischemia: an in vivo study. Exp Neurobiol. 2015;24:41–54.
  • Cavdar Z, Egrilmez MY, Altun ZS, et al. Resveratrol reduces matrix metalloproteinase-2 activity induced by oxygen-glucose deprivation and reoxygenation in human cerebral microvascular endothelial cells. Int J Vitam Nutr Res. 2012;82(4):267–274.
  • He Q, Li S, Li L, et al. Total flavonoids in Caragana (TFC) promotes angiogenesis and enhances cerebral perfusion in a rat model of ischemic stroke. Front Neurosci. 2018;12:635.
  • Sasaki Y, Kobara N, Higashino S, et al. Astaxanthin inhibits thrombosis in cerebral vessels of stroke-prone spontaneously hypertensive rats. Nutr Res. 2011;31(10):784–789.
  • Pan L, Zhou Y, Li XF, et al. Preventive treatment of astaxanthin provides neuroprotection through suppression of reactive oxygen species and activation of antioxidant defense pathway after stroke in rats. Brain Res Bull. 2017;130:211–220.
  • Belousova M, Tokareva OG, Gorodetskaya E, et al. Intravenous treatment with coenzyme Q10 improves neurological outcome and reduces infarct volume after transient focal brain ischemia in rats. J Cardiovasc Pharmacol. 2016;67(2):103–109.
  • Cheng P, Wang L, Ning S, et al. Vitamin E intake and risk of stroke: a meta-analysis. Br J Nutr. 2018;120(10):1181–1188.
  • Bin Q, Hu X, Cao Y, et al. The role of vitamin E (tocopherol) supplementation in the prevention of stroke. A meta-analysis of 13 randomised controlled trials. Thromb Haemost. 2011;105:579–585.
  • Schürks M, Glynn RJ, Rist PM, et al. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ. 2010;341:c5702.
  • Kubota Y, Iso H, Date C, et al. Dietary intakes of antioxidant vitamins and mortality from cardiovascular disease: the Japan Collaborative Cohort Study (JACC) study. Stroke. 2011;42(6):1665–1672.
  • Chen GC, Lu DB, Pang Z, et al. Vitamin C intake, circulating vitamin C and risk of stroke: a meta-analysis of prospective studies. J Am Heart Assoc. 2013;2(6):e000329.
  • Mursu J, Voutilainen S, Nurmi T, et al. Flavonoid intake and the risk of ischaemic stroke and CVD mortality in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Br J Nutr. 2008;100(4):890–895.
  • Hollman PC, Geelen A, Kromhout D. Dietary flavonol intake may lower stroke risk in men and women. J Nutr. 2010;140(3):600–604.
  • Cassidy A, Rimm EB, O’Reilly EJ, et al. Dietary flavonoids and risk of stroke in women. Stroke. 2012;43(4):946–951.
  • Wang ZM, Zhao D, Nie ZL, et al. Flavonol intake and stroke risk: a meta-analysis of cohort studies. Nutrition. 2014;30(5):518–523.
  • Hirvonen T, Virtamo J, Korhonen P, et al. Intake of flavonoids, carotenoids, vitamins C and E, and risk of stroke in male smokers. Stroke. 2000;31(10):2301–2306.
  • Li X, Xu J. Dietary and circulating lycopene and stroke risk: a meta-analysis of prospective studies. Sci Rep. 2014;4:5031.
  • Daviglus ML, Orencia AJ, Dyer AR, et al. Dietary vitamin C, beta-carotene and 30-year risk of stroke: results from the Western Electric Study. Neuroepidemiology. 1997;16(2):69–77.
  • Simani L, Ryan F, Hashemifard S, et al. Serum coenzyme Q10 is associated with clinical neurological outcomes in acute stroke patients. J Mol Neurosci. 2018;66(1):53–58.
  • Ramezani M, Sahraei Z, Simani L, et al. Coenzyme Q10 supplementation in acute ischemic stroke: is it beneficial in short-term administration? Nutr Neurosci. 2018:1–6 doi: 10.1080/1028415X.2018.1541269.
  • Devaraj S, Li D, Jialal I. The effects of alpha tocopherol supplementation on monocyte function. Decreased lipid oxidation, interleukin 1beta secretion, and monocyte adhesion to endothelium. J Clin Invest. 1996;98(3):756–763.
  • Ashor AW, Brown R, Keenan PD, et al. Limited evidence for a beneficial effect of vitamin C supplementation on biomarkers of cardiovascular diseases: an umbrella review of systematic reviews and meta-analyses. Nutr Res. 2019;61:1–12.
  • Moser MA, Chun OK. Vitamin C and heart health: a review based on findings from epidemiologic studies. Int J Mol Sci. 2016;17(8).
  • Putzu A, Daems AM, Lopez-Delgado JC, et al. The effect of vitamin C on clinical outcome in critically ill patients: a systematic review with meta-analysis of randomized controlled trials. Crit Care Med. 2019;47(6):774–783.
  • Rössig L, Hoffmann J, Hugel B, et al. Vitamin C inhibits endothelial cell apoptosis in congestive heart failure. Circulation. 2001;104(18):2182–2187.
  • Martin A, Frei B. Both intracellular and extracellular vitamin C inhibitatherogenic modification of LDL by human vascular endothelial cells. Arterioscler Thromb Vasc Biol. 1997;17(8):1583–1590.
  • Ting HH, Timimi FK, Haley EA, et al. Vitamin C improves endothelium-dependent vasodilation in forearm resistance vessels of humans with hypercholesterolemia. Circulation. 1997;95(12):2617–2622.
  • Heller R, Unbehaun A, Schellenberg B, et al. L-Ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin. J Biol Chem. 2001;276(1):40–47.
  • Nijveldt RJ, van Nood E, van Hoorn DE, et al. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 2001;74(4):418–425.
  • Freedman JE, Parker C 3rd, Li L, et al. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001;103(23):2792–2798.
  • Sudano I, Flammer AJ, Roas S, et al. Cocoa, blood pressure, and vascular function. Curr Hypertens Rep. 2012;14(4):279–284.
  • Larsson SC. Coffee, tea, and cocoa and risk of stroke. Stroke. 2014;45(1):309–314.
  • Giordano P, Scicchitano P, Locorotondo M, et al. Carotenoids and cardiovascular risk. Curr Pharm Des. 2012;18(34):5577–5589.
  • Rissanen TH, Voutilainen S, Nyyssönen K, et al. Low serum lycopene concentration is associated with an excess incidence of acute coronary events and stroke: the Kuopio Ischaemic Heart Disease Risk Factor Study. Br J Nutr. 2001;85(6):749–754.
  • Bahonar A, Saadatnia M, Khorvash F, et al. Carotenoids as potential antioxidant agents in stroke prevention: a systematic review. Int J Prev Med. 2017;8:70.
  • Oude Griep LM, Verschuren WM, Kromhout D, et al. Variety in fruit and vegetable consumption and 10-year incidence of CHD and stroke. Public Health Nutr. 2012;15(12):2280–2286.
  • Palozza P. Prooxidant actions of carotenoids in biologic systems. Nutr Rev. 1998;56(9):257–265.
  • Faulks RM, Hart DJ, Scott KJ, et al. Changes in plasma carotenoid and vitamin E profile during supplementation with oil palm fruit carotenoids. J Lab Clin Med. 1998;132(6):507–511.
  • Littarru GP, Tiano L. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol. 2007;37(1):31–37.
  • Singh JA, Yu S. Allopurinol and the risk of stroke in older adults receiving medicare. BMC Neurol. 2016;16(1):164.
  • Zhang Q, Lan Y, He XF, et al. Allopurinol protects against ischemic insults in a mouse model of cortical microinfarction. Brain Res. 2015;1622:361–367.
  • Dawson J, Quinn TJ, Harrow C, et al. The effect of allopurinol on the cerebral vasculature of patients with subcortical stroke; a randomized trial. Br J Clin Pharmacol. 2009;68(5):662–668.
  • Britnell SR, Chillari KA, Brown JN. The role of xanthine oxidase inhibitors in patients with history of stroke: a systematic review. Curr Vasc Pharmacol. 2018;16(6):583–588.
  • White WB, Saag KG, Becker MA, et al. Cardiovascular safety of febuxostat or allopurinol in patients with gout. N Engl J Med. 2018;378(13):1200–1210.
  • Kojima S, Matsui K, Ogawa H, et al. Rationale, design, and baseline characteristics of a study to evaluate the effect of febuxostat in preventing cerebral, cardiovascular, and renal events in patients with hyperuricemia. J Cardiol. 2017;69(1):169–175.
  • Pluta RM, Rak R, Wink DA, et al. Effects of nitric oxide on reactive oxygen species production and infarction size after brain reperfusion injury. Neurosurgery. 2001;48(4):884–892; discussion 892.
  • Ehlert A, Schmidt C, Wölfer J, et al. Molsidomine for the prevention of vasospasm-related delayed ischemic neurological deficits and delayed brain infarction and the improvement of clinical outcome after subarachnoid hemorrhage: a single-center clinical observational study. J Neurosurg. 2016;124(1):51–58.

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