Abstract
Background: Limited studies concern the influence of obesity-induced dysregulation of adipokines in functional recovery after stroke neurorehabilitation.
Objective: To investigate the relationship between serum leptin, resistin, and adiponectin and functional recovery before and after neurorehabilitation of obese stroke patients. The adipokine potential significance as prognostic markers of rehabilitation outcomes was also verified.
Methods: Twenty obese post-acute stroke patients before and after neurorehabilitation and thirteen obese volunteers without-stroke, as controls, were examined. Adipokines were determined by commercially available enzyme-linked immunosorbent assay (ELISA) kits. Functional deficits were assessed before and after neurorehabilitation with the Barthel Index (BI), modified Rankin Scale (mRS), and Functional Independence Measure (FIM).
Results: Compared to controls, higher leptin and resistin values and lower adiponectin values were observed in stroke patients before neurorehabilitation and no correlations were found between adipokines and clinical outcome measures. Neurorehabilitation was associated with improved scores of BI, mRS, and FIM. After neurorehabilitation, decreased values of Body Mass Index (BMI) and resistin together increased adiponectin were detected in stroke patients, while leptin decreased but not statistically. Comparing adipokine values assessed before neurorehabilitation with the outcome measures after neurorehabilitation, correlations were observed for leptin with BI-score, mRS-score, and FIM-score. No other adipokine levels nor BMI assessed before neurorehabilitation correlated with the clinical measures after neurorehabilitation. The forward stepwise regression analysis identified leptin as prognostic factor for BI, mRS, and FIM.
Conclusion: Our data show the effectiveness of neurorehabilitation in modulating adipokines levels and suggest that leptin could assume the significance of biomarker of functional recovery.
Keywords: Leptin, resistin, adiponectin, obese stroke patients, functional recovery, neurorehabilitation.
[1]
Wang L, Xu F, Brickell A, et al. Additional common loci associated with stroke and obesity identified using pleiotropic analytical approach. Mol Genet Genomics 2020; 295(2): 439‐451.
[2]
Adams KF, Schatzkin A, Harris TB, et al. Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old. N Engl J Med 2006; 355(8): 763-78.
[3]
Kachur S, Lavie CJ, de Schutter A, Milani RV, Ventura HO. Obesity and cardiovascular diseases. Minerva Med 2017; 108(3): 212-28.
[4]
Mozaffarian D, Benjamin E, Go A, et al. Heart disease and stroke statistics-2015 update: A report from the American Heart Association. Circulation 2015; 131(4): e29-322.
[5]
Krishnamurthi RV, Ikeda T, Feigin VL. Global, regional and country-specific burden of ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage: A systematic analysis of the global burden of disease study 2017. Neuroepidemiology 2020; 54(2): 171-9.
[7]
Micera S, Caleo M, Chisari C, Hummel FC, Pedrocchi A. Advanced neurotechnologies for the restoration of motor function. Neuron 2020; 105(4): 604-20.
[8]
MacDonald SL, Shane Journeay W, Uleryk E. A systematic review of the impact of obesity on stroke inpatient rehabilitation functional outcomes. NeuroRehabilitation 2020; 46(3): 403-15.
[9]
Ciancarelli I, Tonin P, Garo ML, Tozzi Ciancarelli MG. Effectiveness of intensive neurorehabilitation in obese subacute stroke patients. Funct Neurol 2019; 34(1): 45-51.
[10]
Kim JH, Choi KH, Kang KW. Impact of visceral adipose tissue on clinical outcomes after acute ischemic stroke. Stroke 2019; 50(2): 448-54.
[11]
Burke DT, Al-Adawi S, Bell RB, Easley K, Chen S, Burke DP. Effect of body mass index on stroke rehabilitation. Arch Phys Med Rehabil 2014; 95(6): 1055-9.
[12]
Doehner W, Schenkel J, Anker SD, Springer J, Audebert HJ. Overweight and obesity are associated with improved survival, functional outcome, and stroke recurrence after acute stroke or transient ischaemic attack: Observations from the TEMPiS trial. Eur Heart J 2013; 34(4): 268-77.
[13]
Nishioka S, Wakabayashi H, Yoshida T, Mori N, Watanabe R, Nishioka E. Obese Japanese patients with stroke have higher functional recovery in convalescent rehabilitation wards: A retrospective cohort study. J Stroke Cerebrovasc Dis 2016; 25(1): 26-33.
[14]
Morone G, Iosa MT, Paolucci T, Muzzioli L, Paolucci S. Relationship between body mass index and rehabilitation outcomes in subacute stroke with dysphagia. Am J Phys Med Rehabil 2019; 98(7): 608-12.
[15]
Jang SY, Shin YI, Kim DY, et al. Effect of obesity on functional outcomes at 6 months post-stroke among elderly Koreans: A prospective multicentre study. BMJ Open 2015; 5(12)e008712
[16]
Kalichman L, Alperovitch-Najenson D, Treger I. The impact of patient’s weight of post-stroke rehabilitation. Disabil Rehabil 2016; 38(17): 1684-90.
[17]
Opatrilova R, Caprnda M, Kubatka P, et al. Adipokines in neurovascular diseases. Biomed Pharmacother 2018; 98: 424-32.
[18]
Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 2007; 56(4): 1010-3.
[19]
Trayhurn P, Wood I. Adipokines: Inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 2004; 92(3): 347-55.
[20]
Seven E, Husemoen LLN, Sehested TSG, et al. Adipocytokines, C-reactive protein, and cardiovascular disease: A population-based prospective study. PLoS One 2015; 10(6)e0128987
[21]
Haley MJ, Lawrence CB. The blood-brain barrier after stroke: Structural studies and the role of transcytotic vesicles. J Cereb Blood Flow Metab 2017; 37(2): 456-70.
[22]
Wolk R, Bertolet M, Singh P, et al. Prognostic value of adipokines in predicting cardiovascular outcome: Explaining the obesity paradox. Mayo Clin Proc 2016; 91(7): 858-66.
[23]
Perovic E, Mrdjen A, Harapin M, Tesija Kuna A, Simundic AM. Diagnostic and prognostic role of resistin and copeptin in acute ischemic stroke. Top Stroke Rehabil 2017; 24(8): 614-8.
[24]
Rubenstein LZ, Stuck AE, Siu AL, Wieland D. Impacts of geriatric evaluation and management programs on defined outcomes: Overview of the evidence. J Am Geriatr Soc 1991; 39(9 Pt 2): 8S-16S. discussion 17S-18S.
[25]
Kaiser MJ, Bauer JM, Ramsch C, et al. Validation of the mini nutritional assessment short-form (MNA®-SF): A practical tool for identification of nutritional status. J Nutr Health Aging 2009; 13(9): 782-.
[26]
World Health Organization. Obesity: Preventing and managing the global epidemic. Report of a WHO consultation (2000). World Health Organ Tech Rep Ser 894; i-xii: 1-153.
[27]
Folstein MF, Folstein SE. MCHugh PR. Mini mental status: A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12(3): 189-98.
[28]
Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Md State Med J 1965; 14: 61-5.
[30]
Chumney D, Nollinger K, Shesko K, Skop K, Spencer M, Newton RA. Ability of functional independence measure to accurately predict functional outcome of stroke-specific population: systematic review. J Rehabil Res Dev 2010; 47(1): 17-29.
[31]
Ciancarelli I, De Amicis D, Di Massimo C, Carolei A, Ciancarelli MG. Oxidative stress in post-acute ischemic stroke patients after intensive neurorehabilitation. Curr Neurovasc Res 2012; 9(4): 266-73.
[32]
Ciancarelli I, De Amicis D, Di Massimo C, Pistarini C, Ciancareli MG. Mean platelet volume during ischemic stroke is a potential pro-inflammatory biomarker in the acute phase and during neurorehabilitation not directly linked to clinical outcome. Curr Neurovasc Res 2016; 13(3): 177-83.
[33]
World Health Organization Obesity: Preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000; 894: i-xii, 1-253.
[35]
Szelenberger R, Kostka J, Saluk-Bijak J, Miller E. Pharmacological interventions and rehabilitation approach for enhancing brain self-repair and stroke recovery. Curr Neuropharmacol 2020; 18(1): 51-64.
[36]
Asgharzade S, Talaei A, Farkhondeh T, Forouzanfar F. Combining growth factor and stem cell therapy for stroke rehabilitation, a review. Curr Drug Targets 2020. [Epub ahead of print].
[37]
Juckett LA, Wengerd LR, Faieta J, Griffin CE. Evidence-based practice implementation in stroke rehabilitation: A scoping review of barriers and facilitators Am J Occup Ther 2020; 74(1) 7401205050p1-p14.
[38]
Jönsson AC, Lindgren I, Norrving B, et al. Weight loss after stroke: A population-based study from the Lund Stroke Register. Stroke 2008; 39(3): 918-23.
[39]
Jayaraj RL, Sheikh A, Rami B, Jalal FY, Rosenberg GA. Neuroinflammation: Friend and foe for ischemic stroke. J Neuroinflam 2019; 16(1): 142.
[40]
Rawlinson C, Jenkins S, Thei L, Dallas ML, Chen R. Post-ischaemic immunological response in the brain: Targeting microglia in ischaemic stroke therapy. Brain Sci 2020; 10(3): 159.
[41]
Ureña-Guerrero ME, Castañeda-Cabral JL, Rivera-Cervantes MC, et al. Neuroprotective and neurestorative effects of Epo and VEGF: Perspectives for new therapeutic approaches to neurological diseases. Curr Pharm Des 2020; 26(12): 1263-76.
[42]
Arboix A, García-Eroles L, Oliveres M, Targa C, Balcells M, Massons J. Pretreatment with statins improves early outcome in patients with first-ever ischaemic stroke: A pleiotropic effect of statins or a beneficial effect of hypercholesterolemia? BMC Neurol 2010; 10: 47.
[43]
Moskowitz MA, Lo EH, Iadecola C. The science of stroke: Mechanisms in search of treatments. Neuron 2010; 67(2): 181-98.
[44]
Iadecola C, Anrather J. The immunology of stroke: From mechanisms to translation. Nat Med 2011; 17(7): 796-808.
[45]
Lakhan SE, Kirchgessner A, Hofer M. Inflammatory mechanisms in ischemic stroke: Therapeutic approaches. J Transl Med 2009; 7: 97.
[46]
Lambertsen KL, Finsen B, Clausen BH. Post-stroke inflammation-target or tool for therapy? Acta Neuropathol 2019; 137(5): 693-714.
[47]
Benakis C, Garcia-Bonilla L, Iadecola C, Anrather J. The role of microglia and myeloid immune cells in acute cerebral ischemia. Front Cell Neurosci 2014; 8: 461.
[48]
Engelhardt B, Sorokin L. The blood–brain and the blood– cerebrospinal fluid barriers: Function and dysfunction. Semin Immunopathol 2009; 31(4): 497-511.
[49]
Haley MJ, Lawrence CB. Obesity and stroke: Can we translate from rodents to patients? J Cereb Blood Flow Metab 2016; 36(12): 2007-21.
[50]
Achike FI, To NH, Wang H, Kwan CY. Obesity, metabolic syndrome, adipocytes and vascular function: A holistic viewpoint. Clin Exp Pharmacol Physiol 2011; 38(1): 1-10.
[51]
Guzik TJ, Marvar PJ, Czesnikiewicz-Guzik M, Korbut R. Perivascular adipose tissue as a messenger of the brain-vessel axis: Role in vascular inflammation and dysfunction. J Physiol Pharmacol 2007; 58(4): 591-610.
[52]
Sorop O, Olver TD, van de Wouw J, et al. The microcirculation: A key player in obesity-associated cardiovascular disease. Cardiovasc Res 2017; 113(9): 1035-45.
[53]
Valerio A, Dossena M, Bertolotti P, et al. Leptin is induced in the ischemic cerebral cortex and exerts neuroprotection through NF-kappaB/c-Rel-dependent transcription. Stroke 2009; 40(2): 610-7.
[54]
Bouziana SD, Tziomalos K, Goulas A, Vyzantiadis TA, Panderi A, Hatzitolios AI. Major adipokines and the -420C>G resistin gene polymorphism as predictors of acute ischemic stroke severity and in-hospital outcome. J Stroke Cerebrovasc Dis 2018; 27(4): 963-70.
[55]
Bloemer J, Pinky PD, Govindarajulu M, et al. Role of adiponectin in central nervous system disorders. Neural Plast 2018; 20184593530
[56]
Avraham Y, Davidi N, Porat M, et al. Leptin reduces infarct size in association with enhanced expression of CB2, TRPV1, SIRT-1 and leptin receptor. Curr Neurovasc Res 2010; 7(2): 136-43.
[57]
Kocot J, Dziemidok P, Kiełczykowska M, Hordyjewska A, Szcześniak G, Musik I. Adipokine profile in patients with type 2 diabetes depends on degree of obesity. Med Sci Monit 2017; 23: 4995-5004.
[58]
Ayeser T, Basak M, Arslan K, Sayan I. Investigating the correlation of the number of diagnostic criteria to serum adiponectin, leptin, resistin, TNF-alpha, EGFR levels and abdominal adipose tissue. Diabetes Metab Syndr 2016; 10(2)(Suppl. 1): S165-9.
[59]
Shen LH, Miao J, Zhao YJ, Liang W. Expression of brain adiponectin in a murine model of transient cerebral ischemia. Int J Clin Exp Med 2014; 7(11): 4590-6.
[60]
Lee TH, Cheng KK, Hoo RL, Siu PM, Yau SY. The novel perspectives of adipokines on brain health. Int J Mol Sci 2019; 20(22): 5638.
[61]
Behrouzifar S, Vakili A, Bandegi AR, Kokhaei P. Neuroprotective nature of adipokine resistin in the early stages of focal cerebral ischemia in a stroke mouse model. Neurochem Int 2018; 114: 99-107.
[62]
Song J, Kang SM, Kim E, Kim CH, Song HT, Lee JE. Adiponectin receptor-mediated signaling ameliorates cerebral cell damage and regulates the neurogenesis of neural stem cells at high glucose concentrations: An in vivo and in vitro study. Cell Death Dis 2015; 6e1844
[63]
Kantorová E, Jesenská Ľ, Čierny D, et al. The intricate network of adipokines and stroke. Int J Endocrinol 2015; 2015967698
[64]
Doherty GH, Oldreive C, Harvey J. Neuroprotective actions of leptin on central and peripheral neurons in vitro. Neuroscience 2008; 154(4): 1297-307.
[65]
Fujita Y, Yamashita T. The effects of leptin on glial cells in neurological diseases. Front Neurosci 2019; 13: 828.
[66]
Meadows KL. Ischemic stroke and select adipose-derived and sex hormones: A review. Hormones (Athens) 2018; 17(2): 167-82.
[67]
Billinger SA, Sisante JV, Mattlage AE, et al. The relationship of pro-inflammatory markers to vascular endothelial function after acute stroke. Int J Neurosci 2017; 127(6): 486-92.
[68]
Bonaventura A, Liberale L, Vecchié A, et al. Update on inflammatory biomarkers and treatments in ischemic stroke. Int J Mol Sci 2016; 17(12): 1967.
[69]
Ragino YI, Stakhneva EM, Polonskaya YV, Kashtanova EV. The role of secretory activity molecules of visceral adipocytes in abdominal obesity in the development of cardiovascular disease: A review. Biomolecules 2020; 10(3): 374.
[70]
Xu T, Li Y, Su Y, Zuo P, Gao Z, Ke K. Serum omentin-1 and risk of one-year mortality in patients with ischemic stroke. Clin Chim Acta 2020; 505: 167-71.
[71]
García-Sánchez A, Gámez-Nava JI, Díaz-de la Cruz EN, et al. The effect of visceral abdominal fat volume on oxidative stress and proinflammatory cytokines in subjects with normal weight, overweight and obesity. Diabetes Metab Syndr Obes 2020; 13: 1077-87.
[72]
Shaafi S, Ebrahimpour-Koujan S, Khalili M, et al. Effects of Alpha Lipoic acid supplementation on serum levels of oxidative stress, inflammatory markers and clinical prognosis among acute ischemic stroke patients: A randomized, double blind, TNS Trial. Adv Pharm Bull 2020; 10(2): 284-9.
[73]
Martha SR, Cheng Q, Fraser JF, et al. Expression of cytokines and chemokines as predictors of stroke outcomes in acute ischemic stroke. Front Neurol 2020; 10: 1391.
[74]
Mo Y, Sun YY, Liu KY. Autophagy and inflammation in ischemic stroke. Neural Regen Res 2020; 15(8): 1388-96.
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