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Cerebrovascular Disease: Consequences of Obesity-Induced Endothelial Dysfunction

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Obesity and Brain Function

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 19))

Abstract

Despite the well-known global impact of overweight and obesity in the incidence of cerebrovascular disease, many aspects of this association are still inconsistently defined. In this chapter we aim to present a critical review on the links between obesity and both ischemic and hemorrhagic stroke and discuss its influence on functional outcomes, survival, and current treatments to acute and chronic stroke. The role of cerebrovascular endothelial function and respective modulation is also described as well as its laboratory and clinical assessment. In this context, the major contributing mechanisms underlying obesity-induced cerebral endothelial function (adipokine secretion, insulin resistance, inflammation, and hypertension) are discussed. A special emphasis is given to the participation of adipokines in the pathophysiology of stroke, namely adiponectin, leptin, resistin, apelin, and visfatin.

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References

  • Abbott NJ, Friedman A (2012) Overview and introduction: the blood-brain barrier in health and disease. Epilepsia 53(Suppl 6):1–6

    Article  PubMed  PubMed Central  Google Scholar 

  • Ainslie PN, Duffin J (2009) Integration of cerebrovascular CO2 reactivity and chemoreflex control of breathing: mechanisms of regulation, measurement, and interpretation. Am J Physiol Regul Integr Comp Physiol 296:R1473–R1495

    Article  CAS  PubMed  Google Scholar 

  • Arrick DM, Sharpe GM, Sun H, Mayhan WG (2007) Diabetes-induced cerebrovascular dysfunction: role of poly(ADP-ribose) polymerase. Microvasc Res 73:1–6

    Article  CAS  PubMed  Google Scholar 

  • Bagi Z, Feher A, Cassuto J (2012) Microvascular responsiveness in obesity: implications for therapeutic intervention. Br J Pharmacol 165:544–560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bang OY, Saver JL, Ovbiagele B, Choi YJ, Yoon SR, Lee KH (2007) Adiponectin levels in patients with intracranial atherosclerosis. Neurology 68:1931–1937

    Article  CAS  PubMed  Google Scholar 

  • Bao H, Yang X, Huang Y, Qiu H, Huang G, Xiao H, Kuai J (2016) The neuroprotective effect of apelin-13 in a mouse model of intracerebral hemorrhage. Neurosci Lett 628:219–224

    Article  CAS  PubMed  Google Scholar 

  • Barseghian A, Gawande D, Bajaj M (2011) Adiponectin and vulnerable atherosclerotic plaques. J Am Coll Cardiol 57:761–770

    Article  CAS  PubMed  Google Scholar 

  • Barton M, Baretella O, Meyer MR (2012) Obesity and risk of vascular disease: importance of endothelium-dependent vasoconstriction. Br J Pharmacol 165:591–602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bazzano LA, Gu D, Whelton MR, Wu X, Chen CS, Duan X et al (2010) Body mass index and risk of stroke among Chinese men and women. Ann Neurol 67:11–20

    Article  PubMed  PubMed Central  Google Scholar 

  • Biffi A, Cortellini L, Nearnberg CM, Ayres AM, Schwab K, Gilson AJ, Rost NS, Goldstein JN, Viswanathan A, Greenberg SM, Rosand J (2011) Body mass index and etiology of intracerebral hemorrhage. Stroke 42(9):2526–2530

    Article  PubMed  PubMed Central  Google Scholar 

  • Bodenant M, Kuulasmaa K, Wagner A, Kee F, Palmieri L, Ferrario MM, Montaye M, Amouyel P, Dallongeville J, MORGAM Project (2011) Measures of abdominal adiposity and the risk of stroke: the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) study. Stroke 42(10):2872–2877

    Article  PubMed  Google Scholar 

  • Boos CJ, Lip GY, Blann AD (2006) Circulating endothelial cells in cardiovascular disease. J Am Coll Cardiol 48:1538–1547

    Article  CAS  PubMed  Google Scholar 

  • Boos CJ, Jaumdally RJ, RJ MF, Varma C, Lip GY (2007) Circulating endothelial cells and von Willebrand factor as indices of endothelial damage/dysfunction in coronary artery disease: a comparison of central vs. peripheral levels and effects of coronary angioplasty. J Thromb Haemost 5:630–632

    Google Scholar 

  • Bounameaux H, John Camm A (2014) Edoxaban: an update on the new oral direct factor Xa inhibitor. Drugs 74(11):1209–1231

    Google Scholar 

  • Bouziana S, Tziomalos K, Goulas A, Ηatzitolios AI (2016) The role of adipokines in ischemic stroke risk stratification. Int J Stroke 11 (4):389–398

    Google Scholar 

  • Branscheidt M, Schneider J, Michel P, Eskioglou E, Kaegi G, Stark R, Fischer U, Jung S, Arnold M, Wertli M, Held U, Wegener S, Luft A, Sarikaya H (2016) No impact of body mass index on outcome in stroke patients treated with IV thrombolysis BMI and IV thrombolysis outcome. PLoS One 11(10):e0164413

    Article  PubMed  PubMed Central  Google Scholar 

  • Brooks SD, DeVallance E, d’Audiffret AC, Frisbee SJ, Tabone LE, Shrader CD, Frisbee JC, Chantler PD (2015) Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats. Am J Physiol Heart Circ Physiol 309:H1846–H1859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burger D, Touyz RM (2012) Cellular biomarkers of endothelial health: microparticles, endothelial progenitor cells, and circulating endothelial cells. J Am Soc Hypertens 6:85–99

    Article  CAS  PubMed  Google Scholar 

  • Calcinaghi N, Wyss MT, Jolivet R, Singh A, Keller AL, Winnik S, Fritschy JM, Buck A, Matter CM, Weber B (2013) Multimodal imaging in rats reveals impaired neurovascular coupling in sustained hypertension. Stroke 44:1957–1964

    Article  PubMed  Google Scholar 

  • Calleja AI, Cortijo E, García-Bermejo P, Reyes J, Bermejo JF, Muñoz MF, Fernandez-Herranz R, Arenillas JF (2013) Blood biomarkers of insulin resistance in acute stroke patients treated with intravenous thrombolysis: Temporal profile and prognostic value. J Diab Res Clin Metab 2(1):2

    Article  CAS  Google Scholar 

  • Campia U, Tesauro M, Cardillo C (2012) Human obesity and endothelium-dependent responsiveness. Br J Pharmacol 165:561–573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Capone C, Faraco G, Park L, Cao X, Davisson RL, Iadecola C (2011) The cerebrovascular dysfunction induced by slow pressor doses of angiotensin II precedes the development of hypertension. Am J Physiol Heart Circ Physiol 300:H397–H407

    Article  CAS  PubMed  Google Scholar 

  • Capone C, Faraco G, Peterson JR, Coleman C, Anrather J, Milner TA, Pickel VM, Davisson RL, Iadecola C (2012a) Central cardiovascular circuits contribute to the neurovascular dysfunction in angiotensin II hypertension. J Neurosci 32:4878–4886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Capone C, Faraco G, Coleman C, Young CN, Pickel VM, Anrather J, Davisson RL, Iadecola C (2012b) Endothelin 1-dependent neurovascular dysfunction in chronic intermittent hypoxia. Hypertension 60:106–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chakrabarti S, Khemka VK, Banerjee A, Chatterjee G, Ganguly A, Biswas A (2015) Metabolic risk factors of sporadic Alzheimer’s disease: implications in the pathology, pathogenesis and treatment. Aging Dis 6:282–299

    Article  PubMed  PubMed Central  Google Scholar 

  • Chan SL, Sweet JG, Bishop N, Cipolla MJ (2016) Pial collateral reactivity during hypertension and aging: understanding the function of collaterals for stroke therapy. Stroke 47:1618–1625

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen X, Zhao S, Song Y, Shi Y, Leak RK, Cao G (2015) The role of nicotinamide phosphoribosyltransferase in cerebral ischemia. Curr Top Med Chem 15(21):2211–2221

    Google Scholar 

  • Cheng Z, Yang X, Wang H (2009) Hyperhomocysteinemia and endothelial dysfunction. Curr Hypertens Rev 5:158–165

    Google Scholar 

  • Chu C, Tokumaru S, Izumi K, Nakagawa K (2016) Obesity increases risk of anticoagulation reversal failure with prothrombin complex concentrate in those with intracranial hemorrhage. Int J Neurosci 126(1):62–66

    Article  CAS  PubMed  Google Scholar 

  • Dahl TB, Yndestad A, Skjelland M, Øie E, Dahl A, Michelsen A, Damås JK, Tunheim SH, Ueland T, Smith C, Bendz B, Tonstad S, Gullestad L, Frøland SS, Krohg-Sørensen K, Russell D, Aukrust P, Halvorsen B (2007) Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization. Circulation 115(8):972–980

    Article  CAS  PubMed  Google Scholar 

  • De Silva TM, Faraci FM (2012) Effects of angiotensin II on the cerebral circulation: role of oxidative stress. Front Physiol 3:484

    Article  PubMed  Google Scholar 

  • Dearborn JL, Schneider AL, Sharrett AR, Mosley TH, Bezerra DC, Knopman DS, Selvin E, Jack CR, Coker LH, Alonso A, Wagenknecht LE, Windham BG, Gottesman RF (2015) Obesity, insulin resistance, and incident small vessel disease on magnetic resonance imaging: atherosclerosis Risk in Communities Study. Stroke 46:3131–3136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deb M, Gerdes S, Heeren M, Lambrecht J, Worthmann H, Goldbecker A, Tryc AB, Lovric S, Schulz-Schaeffer W, Brandis A, Dengler R, Weissenborn K, Haubitz M (2013) Circulating endothelial cells as potential diagnostic biomarkers in primary central nervous system vasculitis. J Neurol Neurosurg Psychiatry 84:732–734

    Article  PubMed  Google Scholar 

  • Delles C, Michelson G, Harazny J, Oehmer S, Hilgers KF, Schmieder RE (2004) Impaired endotelial function of the retinal vasculature in hypertensive patients. Stroke 35:1289–1293

    Article  CAS  PubMed  Google Scholar 

  • Deutsch C, Portik-Dobos V, Smith AD, Ergul A, Dorrance AM (2009) Diet-induced obesity causes cerebral vessel remodeling and increases the damage caused by ischemic stroke. Microvasc Res 78:100–106

    Article  PubMed  PubMed Central  Google Scholar 

  • Didion SP, Sigmund CD, Faraci FM (2000) Impaired endothelial function in transgenic mice expressing both human renin and human angiotensinogen. Stroke 31:760–764

    Article  CAS  PubMed  Google Scholar 

  • Didion SP, Lynch CM, Baumbach GL, Faraci FM (2005) Impaired endothelium-dependent responses and enhanced influence of Rho-kinase in cerebral arterioles in type II diabetes. Stroke 36:342–347

    Article  CAS  PubMed  Google Scholar 

  • Didion SP, Lynch CM, Faraci FM (2007) Cerebral vascular dysfunction in TallyHo mice: a new model of Type II diabetes. Am J Physiol Heart Circ Physiol 292:H1579–H1583

    Article  CAS  PubMed  Google Scholar 

  • Dong XQ, Hu YY, Yu WH, Zhang ZY (2010) High concentrations of resistin in the peripheral blood of patients with acute basal ganglia hemorrhage are associated with poor outcome. J Crit Care 25(2):243–247

    Article  CAS  PubMed  Google Scholar 

  • Dong XQ, Du Q, Yu WH, Zhang ZY, Zhu Q, Che ZH, Wang H, Chen J, Yang SB, Wen JF (2012) Plasma resistin, associated with single nucleotide polymorphism −420, is correlated with C-reactive protein in Chinese Han patients with spontaneous basal ganglia hemorrhage. Genet Mol Res 11(3):1841–1850

    Article  CAS  PubMed  Google Scholar 

  • dos Santos Moreira MC, de Jesus Pinto IS, Mourão AA, Fajemiroye JO, Colombari E, da Silva Reis ÂA, Freiria-Oliveira AH, Ferreira-Neto ML, Pedrino GR (2015) Does the sympathetic nervous system contribute to the pathophysiology of metabolic syndrome? Front Physiol 6:234

    Google Scholar 

  • Drake CT, Iadecola C (2007) The role of neuronal signaling in controlling cerebral blood flow. Brain Lang 102:141–152

    Article  PubMed  Google Scholar 

  • Efstathiou SP, Tsioulos DI, Tsiakou AG, Gratsias YE, Pefanis AV, Mountokalakis TD (2005) Plasma adiponectin levels and five-year survival after first-ever ischemic stroke. Stroke 36(9):1915–1919

    Article  CAS  PubMed  Google Scholar 

  • Efstathiou SP, Tsiakou AG, Tsioulos DI, Panagiotou TN, Pefanis AV, Achimastos AD, Mountokalakis TD (2007) Prognostic significance of plasma resistin levels in patients with atherothrombotic ischemic stroke. Clin Chim Acta 378(1–2):78–85

    Article  CAS  PubMed  Google Scholar 

  • Ergul A, Li W, Elgebaly MM, Bruno A, Fagan SC (2009) Hyperglycemia, diabetes and stroke: focus on the cerebrovasculature. Vasc Pharmacol 51:44–49

    Article  CAS  Google Scholar 

  • Fadini GP, Bonora BM, Marcuzzo G, Marescotti MC, Cappellari R, Pantano G, Sanzari MC, Duran X, Vendrell J, Plebani M, Avogaro A (2015) Circulating stem cells associate with adiposity and future metabolic deterioration in healthy subjects. J Clin Endocrinol Metab 100:4570–4578

    Article  CAS  PubMed  Google Scholar 

  • Faraco G, Iadecola C (2013) Hypertension: a harbinger of stroke and dementia. Hypertension 62:810–817

    Article  CAS  PubMed  Google Scholar 

  • Fierstra J, Sobczyk O, Battisti-Charbonney A, Mandell DM, Poublanc J, Crawley AP, Mikulis DJ, Duffin J, Fisher JA (2013) Measuring cerebrovascular reactivity: what stimulus to use? J Physiol 591:5809–5821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Franceschelli S, Ferrone A, Pesce M, Riccioni G, Speranza L (2013) Biological functional relevance of asymmetric dimethylarginine (ADMA) in cardiovascular disease. Int J Mol Sci 14:24412–24421

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gasbarrino K, Mantzoros C, Gorgui J, Veinot JP, Lai C, Daskalopoulou SS (2016) Circulating chemerin is associated with carotid plaque instability, whereas resistin is related to cerebrovascular symptomatology. Arterioscler Thromb Vasc Biol 36:1670–1678

    Article  CAS  PubMed  Google Scholar 

  • Gorgui J, Gasbarrino K, Georgakis MK, Karalexi MA, Nauche B, Petridou ET, Daskalopoulou SS (2017) Circulating adiponectin levels in relation to carotid atherosclerotic plaque presence, ischemic stroke risk, and mortality: A systematic review and meta-analyses. Metabolism 69:51–66

    Google Scholar 

  • Gostynski M, Gutzwiller F, Kuulasmaa K, Döring A, Ferrario M, Grafnetter D, Pajak A et al (2004) Analysis of the relationship between total cholesterol, age, body mass index among males and females in the WHO MONICA Project. Int J Obes Relat Metab Disord 28:1082–1090

    Article  CAS  PubMed  Google Scholar 

  • Greco SJ, Bryan KJ, Sarkar S, Zhu X, Smith MA, Ashford JW, Johnston JM, Tezapsidis N, Casadesus G (2009) Leptin reduces pathology and improves memory in a transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis 19:1155–1167

    Article  CAS  Google Scholar 

  • Green DJ, Dawson EA, Groenewoud HM, Jones H, Thijssen DH (2014) Is flow-mediated dilation nitric oxide mediated? A meta-analysis. Hypertension 63:376–382

    Article  CAS  PubMed  Google Scholar 

  • Güler E, Babur Güler G, Demir GG, Hatipoğlu S (2015) A review of the fixed dose use of new oral anticoagulants in obese patients: is it really enough? Anatol J Cardiol 15(12):1020–1029

    Article  PubMed  Google Scholar 

  • Hajer GR, van Haeften TW, Visseren FL (2008) Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 29:2959–2971

    Article  CAS  PubMed  Google Scholar 

  • Hart R, Veenstra DL, Boudreau DM, Roth JA (2017) Impact of Body Mass Index and Genetics on Warfarin Major Bleeding Outcomes in a Community Setting. Am J Med 130(2):222–228

    Article  PubMed  Google Scholar 

  • Hata J, Kubo M, Kiyohara Y (2011) Genome-wide association study for ischemic stroke based on the Hisayama study. Nihon Eiseigaku Zasshi 66(1):47–52

    Article  CAS  PubMed  Google Scholar 

  • Hui X, Lam KS, Vanhoutte PM, Xu A (2012) Adiponectin and cardiovascular health: an update. Br J Pharmacol 165:574–590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hund-Georgiadis M, Zysset S, Naganawa S, Norris DG, Yves von Cramon D (2003) Determination of cerebrovascular reactivity by means of fMRI signal changes in cerebral microangiopathy: a correlation with morphological abnormalities. Cerebrovasc Dis 16:158–165

    Article  PubMed  Google Scholar 

  • Iadecola C, Davisson RL (2008) Hypertension and cerebrovascular dysfunction. Cell Metab 7:476–484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Immink RV, van Montfrans GA, Stam J, Karemaker JM, Diamant M, van Lieshout JJ (2005) Dynamic cerebral autoregulation in acute lacunar and middle cerebral artery territory ischemic stroke. Stroke 36:2595–2600

    Article  PubMed  Google Scholar 

  • Jamaluddin MDS, Weakley S, Yao Q, Chen C (2012) Resistin: functional roles and therapeutic considerations for cardiovascular disease. Br J Pharmacol 165:622–632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jennings JR, Muldoon MF, Ryan C, Price JC, Greer P, Sutton-Tyrrell K, van der Veen FM, Meltzer CC (2005) Reduced cerebral blood flow response and compensation among patients with untreated hypertension. Neurology 64:1358–1365

    Article  CAS  PubMed  Google Scholar 

  • John S, Hajj-Ali RA, Min D, Calabrese LH, Cerejo R, Uchino K (2015) Reversible cerebral vasoconstriction syndrome: Is it more than just cerebral vasoconstriction? Cephalalgia 35:631–634

    Article  PubMed  Google Scholar 

  • Kadoglou NP, Fotiadis G, Lambadiari V, Maratou E, Dimitriadis G, Liapis CD (2014) Serum levels of novel adipokines in patients with acute ischemic stroke: potential contribution to diagnosis and prognosis. Peptides 57:12–16

    Article  CAS  PubMed  Google Scholar 

  • Kantorova E, Chomova M, Kurca E, Sivak S, Zelenak K, Kučera P, Galajda P (2011) Leptin, adiponectin and ghrelin, new potential mediators of ischemic stroke. Neuro Endocrinol Lett 32(5):716–721

    CAS  PubMed  Google Scholar 

  • Kantorová E, Jesenská Ľ, Čierny D, Zeleňák K, Sivák Š, Stančík M, Galajda P, Nosáľ V, Kurča E (2015) The intricate network of adipokines and stroke. Int J Endocrinol 2015:967698

    Article  PubMed  PubMed Central  Google Scholar 

  • Katakam PV, Ujhelyi MR, Hoenig ME, Miller AW (1998) Endothelial dysfunction precedes hypertension in diet-induced insulin resistance. Am J Physiol 275:R788–R792 

    Google Scholar 

  • Katsnelson M, Rundek T (2011) Obesity paradox and stroke: noticing the (fat) man behind the curtain. Stroke 42(12):3331–3332

    Article  PubMed  Google Scholar 

  • Kazama K, Wang G, Frys K, Anrather J, Iadecola C (2003) Angiotensin II attenuates functional hyperemia in the mouse somatosensory cortex. Am J Physiol Heart Circ Physiol 285:H1890–H1899

    Article  CAS  PubMed  Google Scholar 

  • Kernan WN, Inzucchi SE, Sawan C, Macko RF, Furie KL (2013) Obesity: a stubbornly obvious target for stroke prevention. Stroke 44(1):278–286

    Article  PubMed  Google Scholar 

  • Kim BJ, Lee SH, Ryu WS, Kim CK, Yoon BW (2012) Adipocytokines and ischemic stroke: differential associations between stroke subtypes. J Neurol Sci 312(1–2):117–122

    Article  CAS  PubMed  Google Scholar 

  • Kim CK, Ryu WS, Choi IY, Kim YJ, Rim D, Kim BJ, Jang H, Yoon BW, Lee SH (2013) Detrimental effects of leptin on intracerebral hemorrhage via the STAT3 signal pathway. J Cereb Blood Flow Metab 33:944–953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kitayama J, Faraci FM, Lentz SR, Heistad DD (2007) Cerebral vascular dysfunction during hypercholesterolemia. Stroke 38:2136–2141

    Article  CAS  PubMed  Google Scholar 

  • Kochanowski J, Grudniak M, Baranowska-Bik A, Wolinska-Witort E, Kalisz M, Baranowska B, Bik W (2012) Resistin levels in women with ischemic stroke. Neuro Endocrinol Lett 33(6):603–607

    CAS  PubMed  Google Scholar 

  • Lee KW, Blann AD, Lip GY (2005) Plasma markers of endothelial damage/dysfunction, inflammation and thrombogenesis in relation to TIMI risk stratification in acute coronary syndromes. Thromb Haemost 94:1077–1083

    CAS  PubMed  Google Scholar 

  • Lee DE, Kehlenbrink S, Lee H, Hawkins M, Yudkin JS (2009) Getting the message across: mechanisms of physiological cross talk by adipose tissue. Am J Physiol Endocrinol Metab 296:E1210–E1229

    Article  CAS  PubMed  Google Scholar 

  • Lind L, Berglund L, Larsson A, Sundstrom J (2011) Endothelial function in resistance and conduit arteries and 5-year risk of cardiovascular disease. Circulation 123:1545–1551

    Article  PubMed  Google Scholar 

  • Little JP, Safdar A (2015) Adipose-brain crosstalk: do adipokines have a role in neuroprotection? Neural Regen Res 10:1381–1382

    Article  PubMed  PubMed Central  Google Scholar 

  • Lo J, Dolan SE, Kanter JR, Hemphill LC, Connelly JM, Lees RS, Grinspoon SK (2006) Effects of obesity, body composition, and adiponectin on carotid intima-media thickness in healthy women. J Clin Endocrinol Metab 91(5):1677–1682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lynch CM, Kinzenbaw DA, Chen X, Zhan S, Mezzetti E, Filosa J, Ergul A, Faulkner JL, Faraci FM, Didion SP (2013) Nox2-derived superoxide contributes to cerebral vascular dysfunction in diet-induced obesity. Stroke 44:3195–3201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Madej A, Okopień B, Kowalski J, Haberka M, Herman ZS (2005) Plasma concentrations of adhesion molecules and chemokines in patients with essential hypertension. Pharmacol Rep 57:878–881

    CAS  PubMed  Google Scholar 

  • Makin AJ, Blann AD, Chung NA, Silverman SH, Lip GY (2004) Assessment of endothelial damage in atherosclerotic vascular disease by quantification of circulating endothelial cells. Relationship with von Willebrand factor and tissue factor. Eur Heart J 25:371–376

    Article  CAS  PubMed  Google Scholar 

  • Mayhan WG, Simmons LK, Sharpe GM (1991) Mechanism of impaired responses of cerebral arterioles during diabetes mellitus. Am J Phys 260(Pt 2):H319–H326

    CAS  Google Scholar 

  • Mayhan WG, Arrick DM, Sharpe GM, Patel KP, Sun H (2006) Inhibition of NAD(P)H oxidase alleviates impaired NOS-dependent responses of pial arterioles in type 1 diabetes mellitus. Microcirculation 13:567–575

    Article  CAS  PubMed  Google Scholar 

  • McDonnell MN, Berry NM, Cutting MA, Keage HA, Buckley JD, Howe PR (2013) Transcranial Doppler ultrasound to assess cerebrovascular reactivity: reliability, reproducibility and effect of posture. Peer J 1:e65

    Article  PubMed  PubMed Central  Google Scholar 

  • Meissner A (2016) Hypertension and the brain: a risk factor for more than heart disease. Cerebrovasc Dis 42(3–4):255–262

    Article  PubMed  Google Scholar 

  • Miao CY, Li ZY (2012) The role of perivascular adipose tissue in vascular smooth muscle cell growth. Br J Pharmacol 165:643–658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Michiels C (2003) Endothelial cell functions. J Cell Physiol 196:430–443

    Article  CAS  PubMed  Google Scholar 

  • Micieli G, Bosone D, Costa A, Cavallini A, Marcheselli S, Pompeo F, Nappi G (1997) Opposite effects of l-arginine and nitroglycerin on cerebral blood velocity: nitric oxide precursors and cerebral blood velocity. J Neurol Sci 150:71–75

    Article  CAS  PubMed  Google Scholar 

  • Micieli G, Bosone D, Zappoli F, Marcheselli S, Argenteri A, Nappi G (1999) Vasomotor response to CO2 and l-Arginine in patients with severe internal carotid artery stenosis; pre- and post-surgical evaluation with transcranial Doppler. J Neurol Sci 163:153–158

    Article  CAS  PubMed  Google Scholar 

  • Miller AA, De Silva TM, Judkins CP, Diep H, Drummond GR, Sobey CG (2010) Augmented superoxide production by Nox2-containing NADPH oxidase causes cerebral artery dysfunction during hypercholesterolemia. Stroke 41:784–789

    Article  CAS  PubMed  Google Scholar 

  • Mochizuki Y, Oishi M, Takasu T (1997) Cerebral blood flow in single and multiple lacunar infarctions. Stroke 28:1458–1460

    Article  CAS  PubMed  Google Scholar 

  • Moreira MC, Pinto IS, Mourão AA, Fajemiroye JO, Colombari E, Reis ÂA, Freiria-Oliveira AH, Ferreira-Neto ML, Pedrino GR (2015) Does the sympathetic nervous system contribute to the pathophysiology of metabolic syndrome? Front Physiol 6:234

    Article  PubMed  PubMed Central  Google Scholar 

  • Murphey HS (2012) Inflammation. In: Streyer R (ed) Rubin’s pathology: clinicopathologic foundations of medicine. Lippincott Williams and Wilkins, Philadelphia, PA, pp 23–44

    Google Scholar 

  • Nishimura M, Izumiya Y, Higuchi A, Shibata R, Qiu J, Kudo C, Shin HK, Moskowitz MA, Ouchi N (2008) Adiponectin prevents cerebral ischemic injury through endothelial nitric oxide synthase dependent mechanisms. Circulation 117:216–223

    Article  CAS  PubMed  Google Scholar 

  • O’Rourke MF, Safar ME (2005) Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension 46:200–204

    Article  PubMed  CAS  Google Scholar 

  • Oesch L, Tatlisumak T, Arnold M, Sarikaya H (2017) Obesity paradox in stroke—Myth or reality? A systematic review. PLoS One 12(3):e0171334

    Article  PubMed  PubMed Central  Google Scholar 

  • Ogorodnikova AD, Wassertheil-Smoller S, Mancuso P, Sowers MR, Rajpathak SN, Allison MA, Baird AE, Rodriguez B, Wildman RP (2010) High-molecular-weight adiponectin and incident ischemic stroke in postmenopausal women: a Women’s Health Initiative Study. Stroke 41(7):1376–1381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ogunsua AA, Touray S, Lui JK, Ip T, Escobar JV, Gore J (2015) Body mass index predicts major bleeding risks in patients on warfarin. J Thromb Thrombolysis 40(4):494–498

    Article  CAS  PubMed  Google Scholar 

  • Okamoto M, Etani H, Yagita Y, Kinoshita N, Nukada T-A (2001) Diminished reserve for cerebral vasomotor response to L-arginine in the elderly: evaluation by transcranial Doppler sonography. Gerontology 47:131–135

    Article  CAS  PubMed  Google Scholar 

  • Osawa H, Doi Y, Makino H, Ninomiya T, Yonemoto K, Kawamura R, Hata J, Tanizaki Y, Iida M, Kiyohara Y (2009) Diabetes and hypertension markedly increased the risk of ischemic stroke associated with high serum resistin concentration in a general Japanese population: the Hisayama Study. Cardiovasc Diabetol 8:60

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Osmond JM, Mintz JD, Dalton B, Stepp DW (2009) Obesity increases blood pressure, cerebral vascular remodeling, and severity of stroke in the Zucker rat. Hypertension 53:381–386

    Article  CAS  PubMed  Google Scholar 

  • Osuka K, Watanabe Y, Yasuda M, Takayasu M (2012) Adiponectin activates endothelial nitric oxide synthase through AMPK signaling after subarachnoid hemorrhage. Neurosci Lett 514(1):2–5

    Article  CAS  PubMed  Google Scholar 

  • Ouchi N, Parker JL, Lugus JJ, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11(2):85–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ovbiagele B, Bath PM, Cotton D, Vinisko R, Diener HC (2011) Obesity and recurrent vascular risk after a recent ischemic stroke. Stroke 42(12):3397–3402

    Article  PubMed  Google Scholar 

  • Palomo I, Marín P, Alarcón M, Gubelin G, Viñambre X, Mora E, Icaza G (2003) Patients with essential hypertension present higher levels of sE-selectin and sVCAM-1 than normotensive volunteers. Clin Exp Hypertens 25:517–523

    Article  CAS  PubMed  Google Scholar 

  • Pantoni L (2010) Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 9:689–701

    Article  PubMed  Google Scholar 

  • Pearson JD (1999) Endothelial cell function and thrombosis. Baillieres Best Pract Res Clin Haematol 12:329–341

    Article  CAS  PubMed  Google Scholar 

  • Perko D, Pretnar-Oblak J, Sabovic M, Zaletel M, Zvan B (2011) Associations between cerebral and systemic endothelial function in migraine patients: a post-hoc study. BMC Neurol 11:146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pescini F, Abbate R (2014) Markers of endothelial dysfunction, oxidative stress, and inflammation in cerebral small vessel disease. In: Gorelick P (ed) Cerebral small vessel disease. Cambridge University Press, Cambridge, pp 192–199

    Chapter  Google Scholar 

  • Pires PW, Dams Ramos CM, Matin N, Dorrance AM (2013) The effects of hypertension on the cerebral circulation. Am J Physiol Heart Circ Physiol 304:H1598–H1614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poggesi A, Pasi M, Pescini F, Pantoni L, Inzitari D (2015) Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: a review. J Cereb Blood Flow Metab 116:1–15

    Google Scholar 

  • Pourcyrous M, Basuroy S, Tcheranova D, Arheart KL, Elabiad MT, Leffler CW, Parfenova H (2015) Brain-derived circulating endothelial cells in peripheral blood of newborn infants with seizures: a potential biomarker for cerebrovascular injury. Physiol Rep 3. doi:10.14814/phy2.12345. pii: e12345

  • Prakash K, Chandran DS, Khadgawat R, Jaryal AK, Deepak KK (2016) Correlations between endothelial function in the systemic and cerebral circulation and insulin resistance in type 2 diabetes mellitus. Diab Vasc Dis Res 13:49–55

    Article  CAS  PubMed  Google Scholar 

  • Prugger C, Luc G, Haas B, Arveiler D, Machez E, Ferrieres J, Ruidavets JB, Bingham A, Montaye M, Amouyel P, Yarnell J, Kee F, Ducimetiere P, Empana JP, PRIME Study Group (2012) Adipocytokines and the risk of ischemic stroke: the PRIME Study. Ann Neurol 71(4):478–486

    Article  CAS  PubMed  Google Scholar 

  • Rajpathak SN, Kaplan RC, Wassertheil-Smoller S, Cushman M, Rohan TE, McGinn AP, Wang T, Strickler HD, Scherer PE, Mackey R, Curb D, Ho GY (2011) Resistin, but not adiponectin and leptin, is associated with the risk of ischemic stroke among postmenopausal women: results from the Women’s Health Initiative. Stroke 42(7):1813–1820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rao A, Pandya V, Whaley-Connell A (2015) Obesity and insulin resistance in resistant hypertension: implications for the kidney. Adv Chronic Kidney Dis 22:211–217

    Article  PubMed  Google Scholar 

  • Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ (2005) Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 111:932–939

    Article  CAS  PubMed  Google Scholar 

  • Rodríguez-Flores M, García-García E, Cano-Nigenda CV, Cantú-Brito C (2014) Relationship of obesity and insulin resistance with the cerebrovascular reactivity: a case control study. Cardiovasc Diabetol 13:2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rosito GA, D’Agostino RB, Massaro J, Lipinska I, Mittleman MA, Sutherland P, Wilson PW, Levy D, Muller JE, Tofler GH (2004) Association between obesity and a prothrombotic state: the Framingham Offspring Study. Thromb Haemost 91:683–689

    CAS  PubMed  Google Scholar 

  • Saber H, Himali JJ, Shoamanesh A, Beiser A, Pikula A, Harris TB, Roubenoff R, Romero JR, Kase CS, Vasan RS, Seshadri S (2015) Serum leptin levels and the risk of stroke: the Framingham Study. Stroke 46(10):2881–2885

    Google Scholar 

  • Sarikaya H, Elmas F, Arnold M, Georgiadis D, Baumgartner RW (2011) Impact of obesity on stroke outcome after intravenous thrombolysis. Stroke 42(8):2330–2332

    Article  PubMed  Google Scholar 

  • Scherbakov N, Dirnagl U, Doehner W (2011) Body weight after stroke: lessons from the obesity paradox. Stroke 42(12):3646–3650

    Article  PubMed  Google Scholar 

  • Seet RC, Zhang Y, Wijdicks EF, Rabinstein AA (2014) Thrombolysis outcomes among obese and overweight stroke patients: an age- and National Institutes of Health Stroke Scale-matched comparison. J Stroke Cerebrovasc Dis 23(1):1–6

    Article  PubMed  Google Scholar 

  • Sena CM, Pereira AM, Seiça R (2013) Endothelial dysfunction—a major mediator of diabetic vascular disease. Biochim Biophys Acta 1832:2216–2231

    Article  CAS  PubMed  Google Scholar 

  • Sena CM, Pereira A, Fernandes R, Letra L, Seiça RM (2017) Adiponectin improves endothelial function in mesenteric arteries of high-fat fed wistar rats: role of perivascular adipose tissue. Br J Pharmacol. doi:10.1111/bph.13756. In press

  • Seo JH, Jeong HY, Noh S, Kim E, Ji K-H, Bae JS et al (2013) Relationship of body mass index and mortality for acute ischemic stroke patients after thrombolysis therapy. J Neurocrit Care 6(2):92–96

    Google Scholar 

  • Serrador JM, Sorond FA, Vyas M, Gagnon M, Iloputaife ID, Lipsitz LA (2005) Cerebral pressure-flow relations in hypertensive elderly humans: transfer gain in different frequency domains. J Appl Physiol 98:151–159

    Article  PubMed  Google Scholar 

  • Shimabukuro M, Higa N, Asahi T, Oshiro Y, Takasu N, Tagawa T, Ueda S, Shimomura I, Funahashi T, Matsuzawa Y (2003) Hypoadiponectinemia is closely linked to endothelial dysfunction in man. J Clin Endocr Metab 88:3236–3240

    Article  CAS  PubMed  Google Scholar 

  • Silventoinen K, Magnusson PK, Tynelius P, Batty GD, Rasmussen F (2009) Association of body size and muscle strength with incidence of coronary heart disease and cerebrovascular diseases: a population-based cohort study of one million Swedish men. Int J Epidemiol 38:110–118

    Article  PubMed  Google Scholar 

  • Söderberg S, Ahrén B, Stegmayr B, Johnson O, Wiklund PG, Weinehall L, Hallmans G, Olsson T (1999) Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort. Stroke 30(2):328–337

    Article  PubMed  Google Scholar 

  • Söderberg S, Stegmayr B, Ahlbeck-Glader C, Slunga-Birgander L, Ahrén B, Olsson T (2003) High leptin levels are associated with stroke. Cerebrovasc Dis 15(1–2):63–69

    Article  PubMed  CAS  Google Scholar 

  • Song YM, Sung J, Davey Smith G, Ebrahim S (2004) Body mass index and ischemic and hemorrhagic stroke: a prospective study in Korean men. Stroke 35:831–836

    Article  PubMed  Google Scholar 

  • Spranger J, Verma S, Göhring I, Bobbert T, Seifert J, Sindler AL, Pfeiffer A, Hileman SM, Tschöp M, Banks WA (2006) Adiponectin does not cross the blood-brain barrier but modifies cytokine expression of brain endothelial cells. Diabetes 55:141–147

    Article  CAS  PubMed  Google Scholar 

  • Stott DJ, Welsh P, Rumley A, Robertson M, Ford I, Sattar N, Westendorp RG, Jukema JW, Cobbe SM, Lowe GD (2009) Adipocytokines and risk of stroke in older people: a nested case-control study. Int J Epidemiol 38(1):253–261

    Article  PubMed  Google Scholar 

  • Strazzullo P, D’Elia L, Cairella G, Garbagnati F, Cappuccio FP, Scalfi L (2010) Excess body weight and incidence of stroke: meta-analysis of prospective studies with 2 million participants. Stroke 41(5):e418–e426

    Article  PubMed  Google Scholar 

  • Suk SH, Sacco RL, Boden-Albala B, Cheun JF, Pittman JG, Elkind MS et al (2003) Abdominal obesity and risk of ischemic stroke: the Northern Manhattan Stroke Study. Stroke 34:1586–1592

    Article  PubMed  Google Scholar 

  • Szmitko PE, Wang CH, Weisel RD, de Almeida JR, Anderson TJ, Verma S (2003) New markers of inflammation and endothelial cell activation: Part I. Circulation 108:1917–1923

    Article  PubMed  Google Scholar 

  • Takeuchi S, Wada K, Otani N, Osada H, Nagatani K, Mori K (2014) Temporal profile of plasma adiponectin level and delayed cerebral ischemia in patients with subarachnoid hemorrhage. J Clin Neurosci 21(6):1007–1010

    Article  CAS  PubMed  Google Scholar 

  • Thorp A, Schlaich MP (2015) Relevance of sympathetic nervous system activation in obesity and metabolic syndrome. J Diabetes Res 2015:341583

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Towfighi A, Ovbiagele B (2009) The impact of body mass index on mortality after stroke. Stroke 40:2704–2708

    Article  PubMed  Google Scholar 

  • Vachharajani V, Cunningham C, Yoza B, Carson J Jr, Vachharajani TJ, McCall C (2012) Adiponectin-deficiency exaggerates sepsis-induced microvascular dysfunction in the mouse brain. Obesity (Silver Spring) 20:498–504

    Article  CAS  Google Scholar 

  • Vaiopoulos AG, Marinou K, Christodoulides C, Koutsilieris M (2012) The role of adiponectin in human vascular physiology. Int J Cardiol 155(2):188–193

    Article  PubMed  Google Scholar 

  • Vemmos K, Ntaios G, Spengos K, Savvari P, Vemmou A, Pappa T et al (2011) Association between obesity and mortality after acute first-ever stroke: the obesity–stroke paradox. Stroke 42:30–36

    Article  PubMed  Google Scholar 

  • Verma S, Li SH, Wang CH, Fedak PW, Li RK, Weisel RD, Mickle DA (2003) Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation 108:736–740

    Article  CAS  PubMed  Google Scholar 

  • Volpe M, Iaccarino G, Vecchione C, Rizzoni D, Russo R, Rubattu S, Condorelli G, Ganten U, Ganten D, Trimarco B, Lindpaintner K (1996) Association and cosegregation of stroke with impaired endothelium-dependent vasorelaxation in stroke prone, spontaneously hypertensive rats. J Clin Invest 98:256–261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wallace JL, Reaves AB, Tolley EA, Oliphant CS, Hutchison L, Alabdan NA, Sands CW, Self TH (2013) Comparison of initial warfarin response in obese patients versus non-obese patients. J Thromb Thrombolysis 36(1):96–101

    Article  CAS  PubMed  Google Scholar 

  • Wan Z, Mah D, Simtchouk S, Kluftinger A, Little JP (2015) Human adipose tissue conditioned media from lean subjects is protective against H2O2 induced neurotoxicity in human SH-SY5Y neuronal cells. Int J Mol Sci 16:1221–1231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang P, Miao CY (2015) NAMPT as a Therapeutic Target against Stroke. Trends Pharmacol Sci 36(12):891–905

    Article  CAS  PubMed  Google Scholar 

  • Wang WH, Yu WH, Dong XQ, Zhang ZY, Zhu Q, Che ZH, Du Q, Wang H (2011) Plasma adiponectin as an independent predictor of early death after acute intracerebral hemorrhage. Clin Chim Acta 412(17–18):1626–1631

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Liu Y, Yang Q, Dai X, Wu S, Wang W et al (2013) Body mass index and risk of total and type-specific stroke in Chinese adults: results from a longitudinal study in China. Int J Stroke 8(4):245–250

    Article  PubMed  Google Scholar 

  • Wannamethee SG, Shaper AG, Whincup PH, Lennon L, Sattar N (2013) Adiposity, adipokines, and risk of incident stroke in older men. Stroke 44(1):3–8

    Article  CAS  PubMed  Google Scholar 

  • Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O’Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Oostenbrugge R, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B, Gorelick PB, Dichgans M, STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1) (2013) Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 12:822–838

    Article  PubMed  PubMed Central  Google Scholar 

  • Weikert C, Westphal S, Berger K, Dierkes J, Möhlig M, Spranger J, Rimm EB, Willich SN, Boeing H, Pischon T (2008) Plasma resistin levels and risk of myocardial infarction and ischemic stroke. J Clin Endocrinol Metab 93(7):2647–2653

    Article  CAS  PubMed  Google Scholar 

  • Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R, Emerging Risk Factors Collaboration (2009) Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 373(9669):1083–1096

    Article  PubMed  Google Scholar 

  • Wiesner G, Brown RE, Robertson GS, Imran SA, Ur E, Wilkinson M (2006) Increased expression of the adipokine genes resistin and fasting-induced adipose factor in hypoxic/ischaemic mouse brain. Neuroreport 17(11):1195–1198

    Article  CAS  PubMed  Google Scholar 

  • Wijnhoud AD, Koudstaal PJ, Dippel DW (2011) The prognostic value of pulsatility index, flow velocity, and their ratio, measured with TCD ultrasound, in patients with a recent TIA or ischemic stroke. Acta Neurol Scand 124:238–244

    Article  CAS  PubMed  Google Scholar 

  • Willie CK, Colino FL, Bailey DM, Tzeng YC, Binsted G, Jones LW, Haykowsky MJ, Bellapart J, Ogoh S, Smith KJ, Smirl JD, Day TA, Lucas SJ, Eller LK, Ainslie PN (2011) Utility of transcranial Doppler ultrasound for the integrative assessment of cerebrovascular function. J Neurosci Methods 196:221–237

    Article  CAS  PubMed  Google Scholar 

  • Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, Crow RS, Curtis JM, Egan CM, Espeland MA, Evans M, Foreyt JP, Ghazarian S, Gregg EW, Harrison B, Hazuda HP, Hill JO, Horton ES, Hubbard VS, Jakicic JM, Jeffery RW, Johnson KC, Kahn SE, Kitabchi AE, Knowler WC, Lewis CE, Maschak-Carey BJ, Montez MG, Murillo A, Nathan DM, Patricio J, Peters A, Pi-Sunyer X, Pownall H, Reboussin D, Regensteiner JG, Rickman AD, Ryan DH, Safford M, Wadden TA, Wagenknecht LE, West DS, Williamson DF, Yanovski SZ, Look AHEAD Research Group (2013) Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 369(2):145–154

    Article  CAS  PubMed  Google Scholar 

  • Winter Y, Rohrmann S, Linseisen J, Lanczik O, Ringleb PA, Hebebrand J, Back T (2008) Contribution of obesity and abdominal fat mass to risk of stroke and transient ischemic attacks. Stroke 39(12):3145–3151

    Article  PubMed  Google Scholar 

  • Woo D, Sekar P, Chakraborty R, Haverbusch MA, Flaherty ML, Kissela BM et al (2005) Genetic epidemiology of intracerebral hemorrhage. J Stroke Cerebrovasc Dis 14:239–243

    Article  PubMed  PubMed Central  Google Scholar 

  • Wormser D, Kaptoge S, Di Angelantonio E, Wood AM, Pennells L, Thompson A, Sarwar N, Kizer JR, Lawlor DA, Nordestgaard BG, Ridker P, Salomaa V, Stevens J, Woodward M, Sattar N, Collins R, Thompson SG, Whitlock G, Danesh J, Emerging Risk Factors Collaboration (2011) Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies. Lancet 377(9771):1085–1095

    Article  PubMed  Google Scholar 

  • Woywodt A, Gerdes S, Ahl B, Erdbruegger U, Haubitz M, Weissenborn K (2012) Circulating endothelial cells and stroke: influence of stroke subtypes and changes during the course of disease. J Stroke Cerebrovasc Dis 21:452–458

    Article  PubMed  Google Scholar 

  • Wu MH, Chio CC, Tsai KJ, Chang CP, Lin NK, Huang CC, Lin MT (2016) Obesity exacerbates rat cerebral ischemic injury through enhancing ischemic adiponectin-containing neuronal apoptosis. Mol Neurobiol 53:3702–3713

    Article  CAS  PubMed  Google Scholar 

  • Wu Y, Wang X, Zhou X, Cheng B, Li G, Bai B (2017) Temporal expression of Apelin/Apelin receptor in ischemic stroke and its therapeutic potential. Front Mol Neurosci 10:1

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Hou Y, Po SS (2015) Obstructive sleep apnoea and atrial fibrillation. Arrhythm Electrophysiol Rev 4(1):14–18

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao QJ, Sun M, Zhang XG, Wang LX (2012) Relationship between serum leptin levels and clinical outcomes of hypertensive intracerebral hemorrhage. Clin Exp Hypertens 34:161–164

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Deng Z, Liao J, Song C, Liang C, Xue H, Wang L, Zhang K, Yan G (2013) Leptin Attenuates Cerebral Ischemia Injury through the Promotion of Energy Metabolism via the PI3K/Akt Pathway. J Cereb Blood Flow Metab 33 (4):567–574

    Google Scholar 

  • Zimmermann C, Wimmer M, Haberl RL (2004) L-arginine mediated vasoreactivity in patients with a risk of stroke. Cerebrovasc Dis 17:128–133

    Article  CAS  PubMed  Google Scholar 

  • Zvan B, Zaletel M, Pogacnik T, Kiauta T (2002) Testing of cerebral endothelium function with l-arginine after stroke. Int Angiol 21:256–259

    CAS  PubMed  Google Scholar 

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Letra, L., Sena, C. (2017). Cerebrovascular Disease: Consequences of Obesity-Induced Endothelial Dysfunction. In: Letra, L., Seiça, R. (eds) Obesity and Brain Function. Advances in Neurobiology, vol 19. Springer, Cham. https://doi.org/10.1007/978-3-319-63260-5_7

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