{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:37:42Z","timestamp":1788583062498,"version":"build-2803163510"},"reference-count":212,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T00:00:00Z","timestamp":1606608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>One of the major obstacles that prevents an effective therapeutic intervention against ischemic stroke is the lack of neuroprotective agents able to reduce neuronal damage; this results in frequent evolution towards a long-term disability with limited alternatives available to aid in recovery. Nevertheless, various treatment options have shown clinical efficacy. Neurotrophins such as brain-derived neurotrophic factor (BDNF), widely produced throughout the brain, but also in distant tissues such as the muscle, have demonstrated regenerative properties with the potential to restore damaged neural tissue. Neurotrophins play a significant role in both protection and recovery of function following neurological diseases such as ischemic stroke or traumatic brain injury. Unfortunately, the efficacy of exogenous administration of these neurotrophins is limited by rapid degradation with subsequent poor half-life and a lack of blood\u2013brain-barrier permeability. Regular exercise seems to be a therapeutic approach able to induce the activation of several pathways related to the neurotrophins release. Exercise, furthermore, reduces the infarct volume in the ischemic brain and ameliorates motor function in animal models increasing astrocyte proliferation, inducing angiogenesis and reducing neuronal apoptosis and oxidative stress. One of the most critical issues is to identify the relationship between neurotrophins and myokines, newly discovered skeletal muscle-derived factors released during and after exercise able to exert several biological functions. Various myokines (e.g., Insulin-Like Growth Factor 1, Irisin) have recently shown their ability to protects against neuronal injury in cerebral ischemia models, suggesting that these substances may influence the degree of neuronal damage in part via inhibiting inflammatory signaling pathways. The aim of this narrative review is to examine the main experimental data available to date on the neuroprotective and anti-ischemic role of regular exercise, analyzing also the possible role played by neurotrophins and myokines.<\/jats:p>","DOI":"10.3390\/ijms21239086","type":"journal-article","created":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T21:00:57Z","timestamp":1606683657000},"page":"9086","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Role of Regular Physical Activity in Neuroprotection against Acute Ischemia"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4529-3703","authenticated-orcid":false,"given":"Domenico","family":"Di Raimondo","sequence":"first","affiliation":[{"name":"Division of Internal Medicine and Stroke Care, Department of Promoting Health, Maternal-Infant. Excellence and Internal and Specialized Medicine (PROMISE) \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine and Stroke Care, Department of Promoting Health, Maternal-Infant. Excellence and Internal and Specialized Medicine (PROMISE) \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Musiari","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine and Stroke Care, Department of Promoting Health, Maternal-Infant. Excellence and Internal and Specialized Medicine (PROMISE) \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Tuttolomondo","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine and Stroke Care, Department of Promoting Health, Maternal-Infant. Excellence and Internal and Specialized Medicine (PROMISE) \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pinto","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine and Stroke Care, Department of Promoting Health, Maternal-Infant. Excellence and Internal and Specialized Medicine (PROMISE) \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,29]]},"reference":[{"key":"ref_1","unstructured":"Riebe, D., Ehrman, J.K., Liguori, G., and Magal, M. (2018). ACM\u2019s Guidelines for Exercise Testing and Prescription, Wolters Kluwer. [10th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1249\/MSS.0b013e3181a0c95c","article-title":"Exercise and physical activity for older adults","volume":"41","author":"Proctor","year":"2009","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e002495","DOI":"10.1161\/JAHA.115.002495","article-title":"Quantifying the Association Between Physical Activity and Cardiovascular Disease and Diabetes: A Systematic Review and Meta-Analysis","volume":"5","author":"Wahid","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.ijcard.2014.12.048","article-title":"Exercise as the master polypill of the 21st century for the prevention of cardiovascular disease","volume":"181","author":"Lucia","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4686","DOI":"10.2174\/1381612822666160510125011","article-title":"Preventive and Therapeutic Role of Muscle Contraction against Chronic Diseases","volume":"22","author":"Musiari","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3390\/ijerph9020391","article-title":"Physical activity and risk of cardiovascular disease--a meta-analysis of prospective cohort studies","volume":"9","author":"Li","year":"2012","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"300","DOI":"10.21037\/atm.2017.07.30","article-title":"New insights about the putative role of myokines in the context of cardiac rehabilitation and secondary cardiovascular prevention","volume":"5","author":"Miceli","year":"2017","journal-title":"Ann. Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"134","DOI":"10.4330\/wjc.v9.i2.134","article-title":"Aerobic vs anaerobic exercise training effects on the cardiovascular system","volume":"9","author":"Patel","year":"2017","journal-title":"World J. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3389\/fcvm.2018.00127","article-title":"Metabolic Mechanisms of Exercise-Induced Cardiac Remodeling","volume":"5","author":"Fulghum","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6578","DOI":"10.1038\/s41598-020-63490-x","article-title":"Resistance training preserves high-intensity interval training induced improvements in skeletal muscle capillarization of healthy old men: A randomized controlled trial","volume":"10","author":"Leuchtmann","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.pmrj.2012.10.007","article-title":"Principles of exercise physiology: Responses to acute exercise and long-term adaptation to training","volume":"4","author":"Frontera","year":"2012","journal-title":"PM R"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1177\/1753944708089701","article-title":"Endurance exercise and resistance training in cardiovascular disease","volume":"2","author":"Meka","year":"2008","journal-title":"Ther. Adv. Cardiovasc. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"97","DOI":"10.5152\/akd.2014.5204","article-title":"The alteration of NTproCNP plasma levels following anaerobic exercise in physically active young men","volume":"15","author":"Vardar","year":"2015","journal-title":"Anatol. J. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1001\/jama.1995.03520290054029","article-title":"Physical activity and public health: A recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine","volume":"273","author":"Pate","year":"1995","journal-title":"JAMA"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"(1996). Physical Activity and Cardiovascular Health: NIH Consensus Development Panel on Physical Activity and Cardiovascular Health. JAMA, 276, 241\u2013246.","DOI":"10.1001\/jama.276.3.241"},{"key":"ref_16","unstructured":"U.S. Department of Health and Human Services (1996). Physical Activity and Health: A Report of the Surgeon General."},{"key":"ref_17","unstructured":"World Health Organization (2010). Global Recommendations on Physical Activity for Health, World Health Organization."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Pelliccia, A., Sharma, S., Gati, S., B\u00e4ck, M., B\u00f6rjesson, M., Caselli, S., Collet, J.P., Corrado, D., Drezner, J.A., and Halle, M. (2020). 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. Eur. Heart J., ehaa605.","DOI":"10.15829\/1560-4071-2021-4488"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1161\/CIRCULATIONAHA.116.018093","article-title":"Exercise Dose in Clinical Practice","volume":"133","author":"Wasfy","year":"2016","journal-title":"Circulation"},{"key":"ref_20","unstructured":"GBD 2015 Neurological Disorders Collaborator Group (2017). Global, regional, and national burden of neurological disorders during 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol., 16, 877\u2013897."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3749","DOI":"10.2174\/1381612822666160428111234","article-title":"Neurotrophic and Neuroprotective Effects of Muscle Contraction","volume":"22","author":"Arnao","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.bbr.2017.06.002","article-title":"At least eighty percent of brain grey matter is modifiable by physical activity: A review study","volume":"332","author":"Batouli","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1016\/j.neubiorev.2013.04.005","article-title":"Beneficial effects of physical exercise on neuroplasticity and cognition","volume":"37","year":"2013","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/22682","article-title":"Ageing, fitness and neurocognitive function","volume":"400","author":"Kramer","year":"1999","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1111\/jnc.14234","article-title":"Cerebral blood flow in normal aging adults: Cardiovascular determinants, clinical implications, and aerobic fitness","volume":"144","author":"Tarumi","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1136\/bjsports-2016-096587","article-title":"Exercise interventions for cognitive function in adults older than 50: A systematic review with meta-analysis","volume":"52","author":"Northey","year":"2017","journal-title":"Br. J. Sports Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3389\/fnagi.2019.00333","article-title":"Aerobic Exercise Training Improves Cerebral Blood Flow and Executive Function: A Randomized, Controlled Cross-Over Trial in Sedentary Older Men","volume":"11","author":"Kleinloog","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1097\/00001756-200312020-00015","article-title":"Exercise activates the endocannabinoid system","volume":"14","author":"Sparling","year":"2003","journal-title":"Neuroreport"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1136\/bjsm.2004.011718","article-title":"Endocannabinoids and exercise","volume":"38","author":"Dietrich","year":"2004","journal-title":"Br. J. Sports Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1016\/j.euroneuro.2016.09.003","article-title":"Chemogenetic activation of dopamine neurons in the ventral tegmental area, but not substantia nigra, induces hyperactivity in rats","volume":"26","author":"Boekhoudt","year":"2016","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1093\/cercor\/bhn013","article-title":"The runner\u2019s high: Opioidergic mechanisms in the human brain","volume":"18","author":"Boecker","year":"2008","journal-title":"Cereb. Cortex"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.cell.2014.07.051","article-title":"Skeletal muscle PGC-1\u03b11 modulates kynurenine metabolism and mediates resilience to stress-induced depression","volume":"159","author":"Agudelo","year":"2014","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.freeradbiomed.2013.04.001","article-title":"Redox signaling in cardiovascular health and disease","volume":"61","author":"Madamanchi","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1002\/jlb.63.6.732","article-title":"Differential regulation of endothelial cell adhesion molecule expression by nitric oxide donors and antioxidants","volume":"63","author":"Spiecker","year":"1998","journal-title":"J. Leukoc. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1089\/ars.2010.3451","article-title":"Mechanistic insight into DNA damage and repair in ischemic stroke: Exploiting the base excision repair pathway as a model of neuroprotection","volume":"14","author":"Li","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1471-4159.1983.tb11284.x","article-title":"Reductions of \u0393-aminobutyric acid and glutamate uptake and (Na++ K+)- ATPase activity in brain slices and Synaptosomes by arachidonic acid","volume":"40","author":"Chan","year":"1983","journal-title":"J. Neurochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1111\/j.1471-4159.1985.tb08755.x","article-title":"Lipid peroxidation-induced inhibition of gamma-aminobutyric acid uptake in rat brain synaptosomes: Protection by glucocorticoids","volume":"44","author":"Braughler","year":"1985","journal-title":"J. Neurochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1097\/00003246-198807000-00015","article-title":"Brain cell death following ischemia and reperfusion: A proposed biochemical sequence","volume":"16","author":"Krause","year":"1988","journal-title":"Crit. Care Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/BF00294614","article-title":"Histological changes of neuronal damage in vegetative dogs induced by 18 minutes of complete global brain ischemia: Two-phase damage of Purkinje cells and hippocampal CA1 pyramidal cells","volume":"80","author":"Sato","year":"1990","journal-title":"Acta Neuropathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3171\/jns.1992.77.2.0169","article-title":"Pathophysiology and treatment of focal cerebral ischemia. Part I: Pathophysiology","volume":"77","year":"1992","journal-title":"J. Neurosurg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1385\/MN:28:3:229","article-title":"Triggers and mediators of hemorrhagic transformation in cerebral ischemia","volume":"28","author":"Wang","year":"2003","journal-title":"Mol. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1161\/hs1101.098653","article-title":"Oxygen radicals in cerebral ischemia: The 2001 Willis lecture","volume":"32","author":"Kontos","year":"2001","journal-title":"Stroke"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/0304-3940(92)90933-X","article-title":"Detection of free radicals during brain ischemia and reperfusion by spin trapping and microdialysis","volume":"138","author":"Zini","year":"1992","journal-title":"Neurosci. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/0006-8993(91)90187-Z","article-title":"Relationship between free radical production and lipid peroxidation during ischemia-reperfusion injury in the rat brain","volume":"554","author":"Sakamoto","year":"1991","journal-title":"Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/sj.jcbfm.9600028","article-title":"Modulation of p53 Degradation via MDM2-Mediated Ubiquitylation and the Ubiquitin\u2013Proteasome System during Reperfusion after Stroke: Role of Oxidative Stress","volume":"25","author":"Saito","year":"2005","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s11064-005-6961-x","article-title":"NF-kappaB in the survival and plasticity of neurons","volume":"30","author":"Mattson","year":"2005","journal-title":"Neurochem. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1016\/j.freeradbiomed.2010.08.010","article-title":"Dysfunctional Nrf2-Keap1 redox signaling in skeletal muscle of the sedentary old","volume":"49","author":"Safdar","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1055\/s-2005-865634","article-title":"Antioxidant status of interval-trained athletes in various sports","volume":"27","author":"Harbula","year":"2006","journal-title":"Int. J. Sports Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.arr.2007.04.004","article-title":"Exercise, oxidative stress and hormesis","volume":"7","author":"Radak","year":"2008","journal-title":"Ageing Res. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.arr.2007.08.007","article-title":"Hormesis defined","volume":"7","author":"Mattson","year":"2008","journal-title":"Ageing Res. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1177\/1559827607300283","article-title":"The Anti-Inflammatory Actions of Exercise Training","volume":"1","author":"Flynn","year":"2007","journal-title":"Am. J. Lifestyle Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1152\/japplphysiol.00562.2005","article-title":"Constitutive pro- and anti-inflammatory cytokine and growth factor response to exercise in leukocytes","volume":"100","author":"Zaldivar","year":"2006","journal-title":"J. Appl. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3622","DOI":"10.2174\/1381612822666160429121934","article-title":"Are the Myokines the Mediators of Physical Activity-Induced Health Benefits?","volume":"22","author":"Tuttolomondo","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev.med.45.1.361","article-title":"Endothelial-leukocyte adhesion molecules in human disease","volume":"45","author":"Bevilacqua","year":"1994","journal-title":"Annu. Rev. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1056\/NEJM199606063342308","article-title":"Adhesion molecules\u2014Part 1","volume":"334","author":"Frenette","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"297","DOI":"10.2147\/JIR.S170262","article-title":"Cell adhesion molecules and exercise","volume":"24","author":"Koh","year":"2018","journal-title":"J. Inflamm. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"C679","DOI":"10.1152\/ajpcell.1994.267.3.C679","article-title":"Shear stress inhibits adhesion of cultured mouse endothelial cells to lymphocytes by downregulating VCAM-1 expression","volume":"267","author":"Ando","year":"1994","journal-title":"Am. J. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ijcard.2004.08.073","article-title":"Exercise training modulates cytokines activity in coronary heart disease patients","volume":"100","author":"Goldhammer","year":"2005","journal-title":"Int. J. Cardiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1161\/01.RES.79.1.32","article-title":"Shear stress modulates expression of Cu\/Zn superoxide dismutase in human aortic endothelial cells","volume":"79","author":"Inoue","year":"1996","journal-title":"Circ. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1161\/01.ATV.18.7.1181","article-title":"Exercise and cardiovascular disease: A new perspective","volume":"18","author":"Santanam","year":"1998","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1161\/01.CIR.91.9.2488","article-title":"Atherosclerosis: Basic mechanisms. Oxidation, inflammation, and genetics","volume":"91","author":"Berliner","year":"1995","journal-title":"Circulation"},{"key":"ref_62","first-page":"6","article-title":"Interleukin-6 in acute exercise and training: What is the biological relevance?","volume":"12","author":"Fischer","year":"2006","journal-title":"Exerc. Immunol. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1097\/00042752-200605000-00009","article-title":"Twenty-four hour ambulatory blood pressure monitoring to evaluate effects on blood pressure of physical activity in hypertensive patients","volume":"16","author":"Pinto","year":"2006","journal-title":"Clin. J. Sport Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1111\/ijcp.12269","article-title":"Metabolic and anti-inflammatory effects of a home-based programme of aerobic physical exercise","volume":"67","author":"Tuttolomondo","year":"2013","journal-title":"Int. J. Clin. Pract."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.3945\/ajcn.2008.26493","article-title":"Accumulating short bouts of brisk walking reduces postprandial plasma triacylglycerol concentrations and resting blood pressure in healthy young men","volume":"88","author":"Miyashita","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1097\/00005768-200209000-00011","article-title":"Accumulating brisk walking for fitness, cardiovascular risk, and psychological health","volume":"34","author":"Murphy","year":"2002","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1152\/japplphysiol.00096.2008","article-title":"Acute moderate-intensity exercise in middle-aged men has neither an anti- nor proinflammatory effect","volume":"105","author":"Markovitch","year":"2008","journal-title":"J. Appl. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nrn848","article-title":"Cross-modal plasticity: Where and how?","volume":"3","author":"Bavelier","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1007\/s12035-020-02021-1","article-title":"A Review of Exercise-Induced Neuroplasticity in Ischemic Stroke: Pathology and Mechanisms","volume":"57","author":"Xing","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"198","DOI":"10.5455\/msm.2012.24.198-202","article-title":"The effect of physical activity on cognition\u2014Physiological mechanisms","volume":"24","author":"Gligoroska","year":"2012","journal-title":"Mater. Sociomed."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1007\/s12640-011-9297-0","article-title":"Influence of physical exercise on traumatic brain injury deficits: Scaffolding effect","volume":"21","author":"Archer","year":"2012","journal-title":"Neurotox. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"104414","DOI":"10.1016\/j.jstrokecerebrovasdis.2019.104414","article-title":"High Intensity Exercise for Walking Competency in Individuals with Stroke: A Systematic Review and Meta-Analysis","volume":"28","author":"Luo","year":"2019","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.rehab.2019.07.006","article-title":"Effect of high-intensity exercise on cardiorespiratory fitness in stroke survivors: A systematic review and meta-analysis","volume":"63","author":"Luo","year":"2020","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1186\/s13063-019-3404-6","article-title":"Real-time foot clearance biofeedback to assist gait rehabilitation following stroke: A randomized controlled trial protocol","volume":"20","author":"Begg","year":"2019","journal-title":"Trials"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e8576","DOI":"10.1590\/1414-431x20198576","article-title":"Effects of physical exercise on skeletal muscles of rats with cerebral ischemia","volume":"52","author":"Melo","year":"2019","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/bs.pmbts.2015.07.004","article-title":"Exercise Regulation of Cognitive Function and Neuroplasticity in the Healthy and Diseased Brain","volume":"135","author":"Hamilton","year":"2015","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.nlm.2006.11.003","article-title":"High impact running improves learning","volume":"87","author":"Winter","year":"2007","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1111\/j.1460-9568.2004.03720.x","article-title":"Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition","volume":"20","author":"Vaynman","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.neuroscience.2003.09.029","article-title":"Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo","volume":"124","author":"Farmer","year":"2004","journal-title":"Neuroscience"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.neuroscience.2006.02.084","article-title":"Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function","volume":"140","author":"Ding","year":"2006","journal-title":"Neuroscience"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1111\/j.1460-9568.2006.05026.x","article-title":"Exercise affects energy metabolism and neural plasticity-related proteins in the hippocampus as revealed by proteomic analysis","volume":"24","author":"Ding","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Di Liegro, C.M., Schiera, G., Proia, P., and Di Liegro, I. (2019). Physical Activity and Brain Health. Genes, 10.","DOI":"10.3390\/genes10090720"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bbr.2004.09.021","article-title":"Exercise, but not environmental enrichment, improves learning after kainic acid-induced hippocampal neurodegeneration in association with an increase in brain-derived neurotrophic factor","volume":"159","author":"Gobbo","year":"2005","journal-title":"Behav. Brain Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.3892\/etm.2013.1319","article-title":"Effect of exercise training on long-term potentiation and NMDA receptor channels in rats with cerebral infarction","volume":"6","author":"Yu","year":"2013","journal-title":"Exp. Ther. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/0092-8674(94)90400-6","article-title":"Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein","volume":"79","author":"Bourtchuladze","year":"1994","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.neuint.2019.04.016","article-title":"Bis(propyl)-cognitin potentiates rehabilitation of treadmill exercise after a transient focal cerebral ischemia, possibly via inhibiting NMDA receptor and regulating VEGF expression","volume":"128","author":"Ke","year":"2019","journal-title":"Neurochem. Int."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1007\/s12035-015-9647-7","article-title":"IGF-1-involved negative feedback of NR2B NMDA subunits protects cultured hippocampal neurons against NMDA-Induced excitotoxicity","volume":"54","author":"Li","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.neuroscience.2014.05.053","article-title":"Pre-ischemic treadmill training alleviates brain damage via GLT-1-mediated signal pathway after ischemic stroke in rats","volume":"274","author":"Wang","year":"2014","journal-title":"Neuroscience"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/brb3.30","article-title":"Beyond vascularization: Aerobic fitness is associated with N-acetylaspartate and working memory","volume":"2","author":"Erickson","year":"2012","journal-title":"Brain Behav."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.pneurobio.2006.12.003","article-title":"N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology","volume":"81","author":"Moffett","year":"2007","journal-title":"Prog. Neurobiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1046\/j.1471-4159.2000.0750453.x","article-title":"Functions of N-acetyl-L-aspartate and N-acetyl-L-aspartylglutamate in the vertebrate brain: Role in glial cell-specific signaling","volume":"75","author":"Baslow","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.neuroscience.2003.08.001","article-title":"Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity","volume":"122","author":"Vaynman","year":"2003","journal-title":"Neuroscience"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1177\/1545968319832605","article-title":"Synergistic Benefits of Combined Aerobic and Cognitive Training on Fluid Intelligence and the Role of IGF-1 in Chronic Stroke","volume":"33","author":"Ploughman","year":"2019","journal-title":"Neurorehabil. Neural Repair"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1177\/1073858418771538","article-title":"Exercise-Induced Neuroplasticity: A Mechanistic Model and Prospects for Promoting Plasticity","volume":"25","author":"Harasym","year":"2019","journal-title":"Neuroscientist"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Avan, A., Digaleh, H., Di Napoli, M., Stranges, S., Behrouz, R., Shojaeianbabaei, G., Amiri, A., Tabrizi, R., Mokhber, N., and Spence, J.D. (2019). Socioeconomic status and stroke incidence, prevalence, mortality, and worldwide burden: An ecological analysis from the Global Burden of Disease Study 2017. BMC Med., 17.","DOI":"10.1186\/s12916-019-1397-3"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-981-10-4304-8_9","article-title":"Clinical Evidence of Exercise Benefits for Stroke","volume":"1000","author":"Han","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1161\/STROKEAHA.115.011238","article-title":"Thromboinflammation in Stroke Brain Damage","volume":"47","author":"Denorme","year":"2016","journal-title":"Stroke"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4289","DOI":"10.2174\/138161212802481200","article-title":"Inflammation in ischemic stroke subtypes","volume":"18","author":"Tuttolomondo","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1093\/eurheartj\/ehw210","article-title":"2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS","volume":"37","author":"Kirchhof","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"8423","DOI":"10.18632\/aging.103149","article-title":"Inflammatory activation and endothelial dysfunction markers in patients with permanent atrial fibrillation: A cross-sectional study","volume":"12","author":"Maida","year":"2020","journal-title":"Aging"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3574","DOI":"10.2174\/138161208786848739","article-title":"Inflammatory cytokines in acute ischemic stroke","volume":"14","author":"Tuttolomondo","year":"2008","journal-title":"Curr. Pharm. Des."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.ejphar.2018.06.028","article-title":"Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches","volume":"833","author":"Shekhar","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jneuroim.2006.11.014","article-title":"The inflammatory response in stroke","volume":"184","author":"Wang","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.2174\/156802609789869619","article-title":"Inflammation as a therapeutic target in acute ischemic stroke treatment","volume":"9","author":"Tuttolomondo","year":"2009","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1161\/01.STR.26.8.1393","article-title":"Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke","volume":"26","author":"Tarkowski","year":"1995","journal-title":"Stroke"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s12974-019-1516-2","article-title":"Neuroinflammation: Friend and foe for ischemic stroke","volume":"16","author":"Jayaraj","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1055\/s-2004-861497","article-title":"Cerebrovascular risk factors and clinical classification of strokes","volume":"4","author":"Pinto","year":"2004","journal-title":"Semin. Vasc. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.atherosclerosis.2016.10.044","article-title":"Endothelial function and arterial stiffness indexes in subjects with acute ischemic stroke: Relationship with TOAST subtype","volume":"256","author":"Tuttolomondo","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4658","DOI":"10.2174\/1381612822666160510124801","article-title":"Inflammation, Endothelial Dysfunction and Arterial Stiffness as Therapeutic Targets in Cardiovascular Medicine","volume":"22","author":"Tuttolomondo","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e813","DOI":"10.1097\/MD.0000000000000813","article-title":"Peripheral frequency of CD4+ CD28-cells in acute ischemic stroke: Relationship with stroke subtype and severity markers","volume":"94","author":"Tuttolomondo","year":"2015","journal-title":"Medicine"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1758-5996-6-28","article-title":"Immune-inflammatory markers and arterial stiffness indexes in subjects with acute ischemic stroke with and without metabolic syndrome","volume":"6","author":"Tuttolomondo","year":"2014","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"824","DOI":"10.2174\/157016111106140128113705","article-title":"Stroke subtypes and their possible implication in stroke prevention drug strategies","volume":"11","author":"Tuttolomondo","year":"2013","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.ijcard.2007.03.109","article-title":"Predictors of outcome in acute ischemic cerebrovascular syndromes: The GIFA study","volume":"125","author":"Tuttolomondo","year":"2008","journal-title":"Int. J. Cardiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1160\/TH08-06-0375","article-title":"Immuno-inflammatory activation in acute cardio-embolic strokes in comparison with other subtypes of ischaemic stroke","volume":"101","author":"Licata","year":"2009","journal-title":"Thromb. Haemost."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1161\/ATVBAHA.107.161240","article-title":"Chemokines and cardiovascular risk","volume":"28","author":"Aukrust","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jns.2008.03.020","article-title":"The impact of inflammation on the pathogenesis and prognosis of ischemic stroke","volume":"15","author":"Nakase","year":"2008","journal-title":"J. Neurol. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Smith, C.J., Emsley, H.C., Gavin, C.M., Georgiou, R.F., Vail, A., Barberan, E.M., del Zoppo, G.J., Hallenbeck, J.M., Rothwell, N.J., and Hopkins, S.J. (2004). Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome. BMC Neurol., 4.","DOI":"10.1186\/1471-2377-4-2"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1161\/01.STR.0000140740.19421.fe","article-title":"Proinflammatory genetic profiles in subjects with history of ischemic stroke","volume":"35","author":"Flex","year":"2004","journal-title":"Stroke"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1080\/01616412.2016.1202395","article-title":"Role of Interleukin-10 (-1082A\/G) gene polymorphism with the risk of ischemic stroke: A meta-analysis","volume":"38","author":"Kumar","year":"2016","journal-title":"Neurol. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.atherosclerosis.2010.08.065","article-title":"Immune-inflammatory markers and arterial stiffness indexes in subjects with acute ischemic stroke","volume":"213","author":"Tuttolomondo","year":"2010","journal-title":"Atherosclerosis"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1161\/01.STR.24.1.35","article-title":"Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment","volume":"24","author":"Adams","year":"1993","journal-title":"Stroke"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"112","DOI":"10.4103\/bc.bc_32_19","article-title":"A brief physical activity protects against ischemic stroke","volume":"5","author":"Zhang","year":"2019","journal-title":"Brain Circ."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3389\/fnagi.2013.00075","article-title":"Shorter term aerobic exercise improves brain, cognition, and cardiovascular fitness in aging","volume":"5","author":"Chapman","year":"2013","journal-title":"Front. Aging Neurosci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1113\/EP086249","article-title":"Regulation of cerebral blood flow and metabolism during exercise","volume":"102","author":"Smith","year":"2017","journal-title":"Exp. Physiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"671","DOI":"10.3233\/JAD-180728","article-title":"Resting Cerebral Blood Flow After Exercise Training in Mild Cognitive Impairment","volume":"67","author":"Alfini","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e2245","DOI":"10.1212\/WNL.0000000000009478","article-title":"Aerobic exercise improves cognition and cerebrovascular regulation in older adults","volume":"94","author":"Guadagni","year":"2020","journal-title":"Neurology"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1159\/000347061","article-title":"Train the vessel, gain the brain: Physical activity and vessel function and the impact on stroke prevention and outcome in cerebrovascular disease","volume":"35","author":"Schmidt","year":"2013","journal-title":"Cerebrovasc. Dis."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.brainres.2014.08.032","article-title":"Treadmill exercise promotes angiogenesis in the ischemic penumbra of rat brains through caveolin-1\/VEGF signaling pathways","volume":"1585","author":"Gao","year":"2014","journal-title":"Brain Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e01079","DOI":"10.1002\/brb3.1079","article-title":"Effects of treadmill exercise on cerebral angiogenesis and MT1-MMP expression after cerebral ischemia in rats","volume":"8","author":"Tang","year":"2018","journal-title":"Brain Behav."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s12017-019-08533-x","article-title":"A Short Bout of Exercise Prior to Stroke Improves Functional Outcomes by Enhancing Angiogenesis","volume":"21","author":"Pianta","year":"2019","journal-title":"Neuromol. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"13684","DOI":"10.1038\/s41598-019-50218-9","article-title":"Early exercise induces long-lasting morphological changes in cortical and hippocampal neurons throughout of a sedentary period of rats","volume":"9","author":"Serra","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.3174\/ajnr.A1695","article-title":"The effect of exercise on the cerebral vasculature of healthy aged subjects as visualized by MR angiography","volume":"30","author":"Bullitt","year":"2009","journal-title":"Am. J. Neuroradiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/cercor\/bhz104","article-title":"Hippocampal Blood Flow Is Increased After 20 min of Moderate-Intensity Exercise","volume":"30","author":"Steventon","year":"2020","journal-title":"Cereb. Cortex"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1298\/ptr.R0006","article-title":"Endogenous neuroprotective potential due to preconditioning exercise in stroke","volume":"22","author":"Sakakima","year":"2019","journal-title":"Phys. Ther. Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1177\/1535370217712691","article-title":"Hypoxic conditioning and the central nervous system: A new therapeutic opportunity for brain and spinal cord injuries?","volume":"242","author":"Baillieul","year":"2017","journal-title":"Exp. Biol. Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1007\/s12035-010-8142-4","article-title":"14-3-3gamma and neuroglobin are new intrinsic protective factors for cerebral ischemia","volume":"41","author":"Dong","year":"2010","journal-title":"Mol. Neurobiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.lfs.2018.03.007","article-title":"High intensity exercise preconditioning provides differential protection against brain injury following experimental stroke","volume":"207","author":"Rezaei","year":"2018","journal-title":"Life Sci."},{"key":"ref_138","first-page":"27","article-title":"Neuroprotective potential of exercise preconditioning in stroke","volume":"1","author":"Islam","year":"2017","journal-title":"Cond. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1212\/01.wnl.0000240057.71766.71","article-title":"Prior TIA, lipid-lowering drug use, and physical activity decrease ischemic stroke severity","volume":"67","author":"Deplanque","year":"2006","journal-title":"Neurology"},{"key":"ref_140","first-page":"614925","article-title":"Previous leisure-time physical activity dose dependently decreases ischemic stroke severity","volume":"2012","author":"Deplanque","year":"2012","journal-title":"Stroke Res. Treat."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bbr.2016.01.049","article-title":"The neuroprotective effects of preconditioning exercise on brain damage and neurotrophic factors after focal brain ischemia in rats","volume":"303","author":"Otsuka","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1016\/j.jstrokecerebrovasdis.2014.01.016","article-title":"The effects of exercise preconditioning on cerebral blood flow change and endothelin-1 expression after cerebral ischemia in rats","volume":"23","author":"Zhang","year":"2014","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1523\/JNEUROSCI.20-08-02926.2000","article-title":"Circulating insulin-like growth factor I mediates effects of exercise on the brain","volume":"20","author":"Carro","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.brainres.2015.07.009","article-title":"Exercise preconditioning improves traumatic brain injury outcomes","volume":"1622","author":"Taylor","year":"2015","journal-title":"Brain Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tins.2007.06.011","article-title":"Exercise builds brain health: Key roles of growth factor cascades and inflammation","volume":"30","author":"Cotman","year":"2007","journal-title":"Trends Neurosci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/oxfordjournals.jbchem.a003231","article-title":"Midkine and pleiotrophin: Two related proteins involved in development, survival, inflammation and tumorigenesis","volume":"132","author":"Muramatsu","year":"2002","journal-title":"J. Biochem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.3389\/fphys.2020.01101","article-title":"Editorial: The Role of the Muscle Secretome in Health and Disease","volume":"11","author":"Aguer","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_148","first-page":"27","article-title":"Neurotrophin-3, TNF-alpha and IL-6 relations in serum and cerebrospinal fluid of ischemic stroke patients","volume":"64","author":"Pasarica","year":"2005","journal-title":"Roum. Arch. Microbiol. Immunol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"765","DOI":"10.2165\/11534530-000000000-00000","article-title":"Neuroplasticity-exercise-induced response of peripheral brain-derived neurotrophic factor: A systematic review of experimental studies in human subjects","volume":"40","author":"Knaepen","year":"2010","journal-title":"Sports Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"R372","DOI":"10.1152\/ajpregu.00525.2009","article-title":"Endurance training enhances BDNF release from the human brain","volume":"298","author":"Seifert","year":"2010","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0165-5728(03)00121-8","article-title":"Basal serum levels and reactivity of nerve growth factor and brain-derived neurotrophic factor to standardized acute exercise in multiple sclerosis and controls","volume":"138","author":"Gold","year":"2003","journal-title":"J. Neuroimmunol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jns.2007.12.030","article-title":"Serum brain-derived neurotrophic factor response to aerobic exercise in multiple sclerosis","volume":"269","author":"Castellano","year":"2008","journal-title":"J. Neurol. Sci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1113\/expphysiol.2009.048512","article-title":"Evidence for a release of brain-derived neurotrophic factor from the brain during exercise","volume":"94","author":"Rasmussen","year":"2009","journal-title":"Exp. Physiol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1098\/rstb.2006.1894","article-title":"Neurotrophin-regulated signalling pathways","volume":"361","author":"Reichardt","year":"2006","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1007\/s00125-009-1364-1","article-title":"Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase","volume":"52","author":"Matthews","year":"2009","journal-title":"Diabetologia"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.bbr.2018.11.037","article-title":"Effect of aerobic exercise on BDNF\/proBDNF expression in the ischemic hippocampus and depression recovery of rats after stroke","volume":"362","author":"Luo","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1152\/jn.00152.2002","article-title":"Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity","volume":"88","author":"Ying","year":"2002","journal-title":"J. Neurophysiol."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Shih, P.C., Yang, Y.R., and Wang, R.Y. (2013). Effects of exercise intensity on spatial memory performance and hippocampal synaptic plasticity in transient brain ischemic rats. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078163"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1249\/mss.0b013e31802f04c7","article-title":"The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function","volume":"39","author":"Ferris","year":"2007","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.brainres.2006.08.105","article-title":"Acute BDNF and cortisol response to low intensity exercise and following ramp incremental exercise to exhaustion in humans","volume":"1121","author":"Schmidt","year":"2006","journal-title":"Brain Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.neulet.2007.11.019","article-title":"Influence of exercise on serum brain-derived neurotrophic factor concentrations in healthy human subjects","volume":"431","author":"Tang","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1097\/WNR.0b013e32835946ca","article-title":"Kinetics of serum brain-derived neurotrophic factor following low-intensity versus high-intensity exercise in men and women","volume":"23","author":"Otterbein","year":"2012","journal-title":"Neuroreport"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s10974-012-9302-0","article-title":"Current evidence that exercise can increase the number of adult stem cells","volume":"33","author":"Macaluso","year":"2012","journal-title":"J. Muscle Res. Cell Motil."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.neulet.2010.05.058","article-title":"Training augments resistance exercise induced elevation of circulating brain derived neurotrophic factor (BDNF)","volume":"479","author":"Yarrow","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref_165","first-page":"119","article-title":"Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men","volume":"59","author":"Zoladz","year":"2008","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.neurobiolaging.2009.08.001","article-title":"Physical activity and memory functions: An interventional study","volume":"32","author":"Ruscheweyh","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jns.2004.06.009","article-title":"Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis","volume":"225","author":"Schulz","year":"2004","journal-title":"J. Neurol. Sci."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1590\/S1807-59322010001100012","article-title":"Acute strength exercise and the involvement of small or large muscle mass on plasma brain-derived neurotrophic factor levels","volume":"65","author":"Correia","year":"2010","journal-title":"Clinics"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00421-010-1461-3","article-title":"Strength training does not influence serum brain-derived neurotrophic factor","volume":"110","author":"Goekint","year":"2010","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1055\/s-0028-1093322","article-title":"Effects of strength and endurance training on brain-derived neurotrophic factor and insulin-like growth factor 1 in humans","volume":"41","author":"Schiffer","year":"2009","journal-title":"Horm. Metab. Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1249\/MSS.0b013e31815dd057","article-title":"BDNF, metabolic risk factors, and resistance training in middle-aged individuals","volume":"40","author":"Levinger","year":"2008","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_172","first-page":"533","article-title":"The effect of physical activity on the brain derived neurotrophic factor: From animal to human studies","volume":"61","author":"Zoladz","year":"2010","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"e15092","DOI":"10.7554\/eLife.15092","article-title":"Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body beta-hydroxybutyrate","volume":"5","author":"Sleiman","year":"2016","journal-title":"eLife"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.cmet.2016.05.025","article-title":"Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function","volume":"24","author":"Moon","year":"2016","journal-title":"Cell Metab."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41591-018-0275-4","article-title":"Exercise-linked FNDC5\/irisin rescues synaptic plasticity and memory defects in Alzheimer\u2019s models","volume":"25","author":"Lourenco","year":"2019","journal-title":"Nat. Med."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jpsychires.2014.10.003","article-title":"A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor","volume":"60","author":"Szuhany","year":"2015","journal-title":"J. Psychiatr. Res."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Dinoff, A., Herrmann, N., Swardfager, W., Liu, C.S., Sherman, C., Chan, S., and Lanct\u00f4t, K.L. (2016). The Effect of Exercise Training on Resting Concentrations of Peripheral Brain-Derived Neurotrophic Factor (BDNF): A Meta-Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163037"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.pneurobio.2009.07.008","article-title":"Circulating insulin-like growth factor I and cognitive function: Neuromodulation throughout the lifespan","volume":"89","author":"Aleman","year":"2009","journal-title":"Prog. Neurobiol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s12975-014-0357-7","article-title":"The effects of poststroke aerobic exercise on neuroplasticity: A systematic review of animal and clinical studies","volume":"6","author":"Ploughman","year":"2015","journal-title":"Transl. Stroke Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.neures.2014.06.007","article-title":"Aerobic exercise effects on neuroprotection and brain repair following stroke: A systematic review and perspective","volume":"87","author":"Austin","year":"2014","journal-title":"Neurosci. Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.2522\/ptj.20130053","article-title":"Promoting neuroplasticity for motor rehabilitation after stroke: Considering the effects of aerobic exercise and genetic variation on brain-derived neurotrophic factor","volume":"93","author":"Mang","year":"2013","journal-title":"Phys. Ther."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1016\/j.jstrokecerebrovasdis.2014.01.015","article-title":"Changes in serum growth factors in stroke rehabilitation patients and their relation to hemiparesis improvement","volume":"23","author":"Okazaki","year":"2014","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1249\/MSS.0b013e3181b07c4d","article-title":"Insulin-like growth factor I as a biomarker of health, fitness, and training status","volume":"42","author":"Nindl","year":"2010","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_184","first-page":"50","article-title":"Exercise and circulating insulin-like growth factor I","volume":"62","author":"Berg","year":"2004","journal-title":"Horm. Res."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1055\/s-0030-1267950","article-title":"Effect of resistance exercise on serum levels of growth factors in humans","volume":"42","author":"Knicker","year":"2010","journal-title":"Horm. Metab. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1055\/s-0029-1242811","article-title":"Serum basal hormone concentrations, nutrition and physical fitness during strength and\/or endurance training in 39-64-year-old women","volume":"31","author":"Laaksonen","year":"2010","journal-title":"Int. J. Sports Med."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1152\/jappl.1994.76.6.2490","article-title":"Effect of brief exercise on circulating insulin-like growth factor I","volume":"76","author":"Cappon","year":"1994","journal-title":"J. Appl. Physiol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ghir.2010.03.004","article-title":"Brief, high intensity exercise alters serum ghrelin and growth hormone concentrations but not IGF-I, IGF-II or IGF-I bioactivity","volume":"20","author":"Stokes","year":"2010","journal-title":"Growth Horm. IGF Res."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1249\/MSS.0b013e3181b07d2d","article-title":"Exercise and the growth hormone-insulin-like growth factor axis","volume":"42","author":"Frystyk","year":"2010","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/cne.901240303","article-title":"Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats","volume":"124","author":"Altman","year":"1965","journal-title":"J. Comp. Neurol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1126\/science.887941","article-title":"Neurogenesis in the adult rat: Electron microscopic analysis of light radioautographs","volume":"197","author":"Kaplan","year":"1977","journal-title":"Science"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1038\/3305","article-title":"Neurogenesis in the adult human hippocampus","volume":"4","author":"Eriksson","year":"1998","journal-title":"Nat. Med."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.brainres.2011.08.012","article-title":"Alteration of protein expression profile following voluntary exercise in the perilesional cortex of rats with focal cerebral infarction","volume":"1416","author":"Mizutani","year":"2011","journal-title":"Brain Res."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"5678","DOI":"10.1523\/JNEUROSCI.21-15-05678.2001","article-title":"Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy","volume":"21","author":"Carro","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1097\/00004647-200003000-00010","article-title":"The window of opportunity for neuronal rescue with insulin-like growth factor-1 after hypoxia-ischemia in rats is critically modulated by cerebral temperature during recovery","volume":"20","author":"Guan","year":"2000","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0306-4522(01)00145-2","article-title":"Insulin-like growth factor-1 improves somatosensory function and reduces the extent of cortical infarction and ongoing neuronal loss after hypoxia-ischemia in rats","volume":"105","author":"Guan","year":"2001","journal-title":"Neuroscience"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S0006-8993(01)03148-1","article-title":"Neuroprotective effects of the N-terminal tripeptide of IGF-1, glycine-proline-glutamate, in the immature rat brain after hypoxic-ischemic injury","volume":"922","author":"Sizonenko","year":"2001","journal-title":"Brain Res."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1097\/01.WCB.0000067720.12805.6F","article-title":"Insulin-like growth factor (IGF)-1 suppresses oligodendrocyte caspase-3 activation and increases glial proliferation after ischemia in near-term fetal sheep","volume":"23","author":"Cao","year":"2003","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_199","first-page":"575","article-title":"The effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain ageing","volume":"197","author":"Sonntag","year":"2000","journal-title":"J. Anat."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature10777","article-title":"A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis","volume":"481","author":"Bostrom","year":"2012","journal-title":"Nature"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.cmet.2013.09.008","article-title":"Exercise induces hippocampal BDNF through a PGC-1alpha\/FNDC5 pathway","volume":"18","author":"Wrann","year":"2013","journal-title":"Cell Metab."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.metabol.2016.12.003","article-title":"The novel exercise-induced hormone irisin protects against neuronal injury via activation of the Akt and ERK1\/2 signaling pathways and contributes to the neuroprotection of physical exercise in cerebral ischemia","volume":"68","author":"Li","year":"2017","journal-title":"Metabolism"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.molimm.2017.09.014","article-title":"Irisin protects against neuronal injury induced by oxygen-glucose deprivation in part depends on the inhibition of ROS-NLRP3 inflammatory signaling pathway","volume":"91","author":"Peng","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"9070341","DOI":"10.1155\/2018\/9070341","article-title":"Irisin exerts neuroprotective effects on cultured neurons by regulating astrocytes","volume":"2018","author":"Wang","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1161\/STROKEAHA.113.001447","article-title":"Serum brain-derived neurotrophic factor and vascular endothelial growth factor levels are associated with risk of stroke and vascular brain injury: Framingham Study","volume":"44","author":"Pikula","year":"2013","journal-title":"Stroke"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"532","DOI":"10.3389\/fncel.2018.00532","article-title":"High-Altitude Cognitive Impairment Is Prevented by Enriched Environment Including Exercise via VEGF Signaling","volume":"12","author":"Bengoetxea","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.nbd.2012.08.020","article-title":"Endogenous CNTF mediates stroke-induced adult CNS neurogenesis in mice","volume":"49","author":"Kang","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12933-015-0229-9","article-title":"Serum fibroblast growth factor 21 levels are related to subclinical atherosclerosis in patients with type 2 diabetes","volume":"14","author":"Xiao","year":"2015","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S0306-4522(02)00989-2","article-title":"Neuroprotection associated with running: Is it a result of increased endogenous neurotrophic factors?","volume":"118","author":"Ang","year":"2003","journal-title":"Neuroscience"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.neulet.2012.09.021","article-title":"Treadmill rehabilitation treatment enhanced BDNF-TrkB but not NGF-TrkA signaling in a mouse intracerebral hemorrhage model","volume":"529","author":"Chen","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1126\/science.7770776","article-title":"Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons","volume":"268","author":"Funakoshi","year":"1995","journal-title":"Science"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.neuroscience.2005.08.037","article-title":"Endurance exercise regimens induce differential effects on brain-derived neurotrophic factor, synapsin-I and insulin-like growth factor I after focal ischemia","volume":"136","author":"Ploughman","year":"2005","journal-title":"Neuroscience"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/9086\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:39:12Z","timestamp":1760179152000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/9086"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,29]]},"references-count":212,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21239086"],"URL":"https:\/\/doi.org\/10.3390\/ijms21239086","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,29]]}}}