Post-stroke BDNF Concentration Changes Following Physical Exercise: A Systematic Review

Carolina C Alcantara, Luisa F García-Salazar, Marcela A Silva-Couto, Gabriela L Santos, Darcy S Reisman, Thiago L Russo, Carolina C Alcantara, Luisa F García-Salazar, Marcela A Silva-Couto, Gabriela L Santos, Darcy S Reisman, Thiago L Russo

Abstract

Background: Research over the last two decades has highlighted the critical role of Brain-derived neurotrophic factor (BDNF) in brain neuroplasticity. Studies suggest that physical exercise may have a positive impact on the release of BDNF and therefore, brain plasticity. These results in animal and human studies have potential implications for the recovery from damage to the brain and for interventions that aim to facilitate neuroplasticity and, therefore, the rehabilitation process. Purpose: The aim of this study was to carry out a systematic review of the literature investigating how aerobic exercises and functional task training influence BDNF concentrations post-stroke in humans and animal models. Data Sources: Searches were conducted in PubMed (via National Library of Medicine), SCOPUS (Elsevier), CINAHL with Full Text (EBSCO), MEDLINE 1946-present with daily updates (Ovid) and Cochrane. Study Selection: All of the database searches were limited to the period from January, 2004 to May, 2017. Data Extraction: Two reviewers extracted study details and data. The methodological quality of the studies that used animal models was assessed using the ARRIVE Guidelines, and the study that evaluated human BDNF was assessed using the PEDro Scale. Data Synthesis: Twenty-one articles were included in this review. BDNF measurements were performed systemically (serum/plasma) or locally (central nervous system). Only one study evaluated human BDNF concentrations following physical exercise, while 20 studies were experimental studies using a stroke model in animals. A wide variation was observed in the training protocol between studies, although treadmill walking was the most common type of intervention among the studies. Studies were of variable quality: the studies that used animal models scored from 8/20 to 15/20 according to the ARRIVE Guidelines. The only study that evaluated human subjects scored 5/10 according to the PEDro scale and, which indicates a quality classified as "fair". Conclusions: The results of the current systematic review suggest that aerobic exercise promotes changes in central BDNF concentrations post-stroke. On the other hand, BDNF responses following functional exercises, such as reaching training and Constraint Induced Movement Therapy (CIMT), seem to be still controversial. Given the lack of studies evaluating post-stroke BDNF concentration following physical exercise in humans, these conclusions are based on animal work.

Keywords: Brain-derived neurotrophic factor; exercise; neuroplasticity; rehabilitation; stroke.

Figures

Figure 1
Figure 1
Flowchart for literature search.

References

    1. Binder DK, Scharfman HE. Brain-derived neurotrophic factor. Growth Factors (2004) 22:123–31. 10.1080/08977190410001723308
    1. Baydyuk M, Xu B. BDNF signaling and survival of striatal neurons. Front. Cell. Neurosci. (2014) 8:254. 10.3389/fncel.2014.00254
    1. Schäbitz WR, Steigleder T, Cooper-Kuhn CM, Schwab S, Sommer C, Schneider A, et al. . Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor recovery and stimulates neurogenesis. Stroke (2007) 38:2165–72. 10.1161/STROKEAHA.106.477331
    1. Ploughman M, Windle V, MacLellan CL, White N, Doré JJ, Corbett D. Brain-derived neurotrophic factor contributes to recovery of skilled reaching after focal ischemia in rats. Stroke (2009) 40:1490–5. 10.1161/STROKEAHA.108.531806
    1. Andreska T, Aufmkolk S, Sauer M, Blum R. High abundance of BDNF within glutamatergic presynapses of cultured hippocampal neurons. Front Cell Neurosci. (2014) 8:107. 10.3389/fncel.2014.00107
    1. Murer MG, Boissiere F, Yan Q, Hunot S, Villares J, Faucheux B, et al. . An immunohistochemical study of the distribution of brain-derived neurotrophic factor in the adult human brain, with particular reference to Alzheimer's disease. Neuroscience (1999) 88:1015–32. 10.1016/S0306-4522(98)00219-X
    1. Austin MW, Ploughman M, Glynn L, Corbett D. Aerobic exercise effects on neuroprotection and brain repair following stroke: a systematic review and perspective. Neurosci Res. (2014) 87:8–15. 10.1016/j.neures.2014.06.007
    1. Ploughman M, Austin MW, Glynn L, Corbett D. The effects of poststroke aerobic exercise on neuroplasticity: a systematic review of animal and clinical studies. Transl Stroke Res. (2015) 6:13–28. 10.1007/s12975-014-0357-7
    1. Kellner Y, Gödecke N, Dierkes T, Thieme N, Zagrebelsky M, Korte M. The BDNF effects on dendritic spines of mature hippocampal neurons depend on neuronal activity. Front Synapt Neurosci. (2014) 6:5. 10.3389/fnsyn.2014.00005
    1. Mang CS, Campbell KL, Ross CJ, Boyd LA. Promoting neuroplasticity for motor rehabilitation after stroke: considering the effects of aerobic exercise and genetic variation on brain-derived neurotrophic factor. Physical Therapy (2013) 93:1707–16. 10.2522/ptj.20130053
    1. Angevaren M, Aufdemkampe G, Verhaar HJ, Aleman A, Vanhees L. Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment. Cochr Database Syst Rev. (2008) CD005381. 10.1002/14651858.CD005381.pub3
    1. Knaepen K, Goekint M, Heyman EM, Meeusen R. Neuroplasticity - exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects. Sports Med. (2010) 40:765–801. 10.2165/11534530-000000000-00000
    1. Dinoff A, Herrmann N, Swardfager W, Liu CS, Sherman C, Chan S, et al. . The effect of exercise training on resting concentrations of peripheral brain-derived neurotrophic factor (BDNF): a meta-analysis. PLoS ONE (2016) 11:e0163037. 10.1371/journal.pone.0163037
    1. Kim MW, Bang MS, Han TR, Ko YJ, Yoon BW, Kim JH, et al. . Exercise increased BDNF and trkB in the contralateral hemisphere of the ischemic rat brain. Brain Res. (2005) 1052:16–21. 10.1016/j.brainres.2005.05.070
    1. Zhang QW, Deng XX, Sun X, Xu JX, Sun FY. Exercise promotes axon regeneration of newborn striatonigral and corticonigral projection neurons in rats after ischemic stroke. PLoS ONE (2013) 8:e80139. 10.1371/journal.pone.0080139
    1. Banoujaafar H, Van Hoecke J, Mossiat CM, Marie C. Brain BDNF levels elevation induced by physical training is reduced after unilateral common carotid artery occlusion in rats. J Cereb Blood Flow Metab. (2014) 34:1681–7. 10.1038/jcbfm.2014.133
    1. Ishida A, Misumi S, Ueda Y, Shimizu Y, Cha-Gyun J, Tamakoshi K, et al. . Early constraint-induced movement therapy promotes functional recovery and neuronal plasticity in a subcortical hemorrhage model rat. Behav Brain Res. (2015) 284:158–66. 10.1016/j.bbr.2015.02.022
    1. Livingston-Thomas JM, Hume AW, Doucette TA, Tasker RA. A novel approach to induction and rehabilitation of deficits in forelimb function in a rat model of ischemic stroke. Acta Pharmacol Sin. (2013) 34:104–12. 10.1038/aps.2012.106
    1. El-Tamawy MS, Abd-Allah F, Ahmed SM, Darwish MH, Khalifa HA. Aerobic exercises enhance cognitive functions and brain derived neurotrophic factor in ischemic stroke patients. NeuroRehabilitation. (2014) 34:209–13. 10.3233/NRE-131020
    1. Maher CG, Sherrington C, Herbert RD, Moseley AM, Elkins M. Reliability of the PEDro scale for rating quality of randomized controlled trials. Phys Ther. (2003) 83:713–21. 10.1093/ptj/83.8.713
    1. Ploughman M, Granter-Button S, Chernenko G, Tucker BA, Mearow KM, Corbett D. Endurance exercise regimens induce differential effects on brain-derived neurotrophic factor, synapsin-I and insulin-like growth factor I after focal ischemia. Neuroscience (2005) 136:991–1001. 10.1016/j.neuroscience.2005.08.037
    1. Ploughman M, Granter-Button S, Chernenko G, Attwood Z, Tucker BA, Mearow KM, et al. . Exercise intensity influences the temporal profile of growth factors involved in neuronal plasticity following focal ischemia. Brain Res. (2007) 1150:207–16. 10.1016/j.brainres.2007.02.065
    1. Ke Z, Yip SP, Li L, Zheng XX, Tong KY. The effects of voluntary, involuntary, and forced exercises on brain-derived neurotrophic factor and motor function recovery: a rat brain ischemia model. PLoS ONE (2011) 6:e16643. 10.1371/journal.pone.0016643
    1. Chen J, Qin J, Su Q, Liu Z, Yang J. Treadmill rehabilitation treatment enhanced BDNF-TrkB but not NGF-TrkA signaling in a mouse intracerebral hemorrhage model. Neurosci Lett. (2012) 529:28–32. 10.1016/j.neulet.2012.09.021
    1. Quirié A, Hervieu M, Garnier P, Demougeot C, Mossiat C, Bertrand N, et al. . Comparative effect of treadmill exercise on mature BDNF production in control versus stroke rats. PLoS ONE (2012) 7:e44218. 10.1371/journal.pone.0044218
    1. Lan X, Zhang M, Yang W, Zheng Z, Wu Y, Zeng Q, et al. . Effect of treadmill exercise on 5-HT, 5-HT1A receptor and brain derived neurophic factor in rats after permanent middle cerebral artery occlusion. Neurol. Sci. (2014) 35:761–6. 10.1007/s10072-013-1599-y
    1. Seo TB, Kim TW, Shin MS, Ji ES, Cho HS, Lee JM, et al. . Aerobic exercise alleviates ischemia-induced memory impairment by enhancing cell proliferation and suppressing neuronal apoptosis in hippocampus. Int. Neurourol. J. (2014) 18:187–97. 10.5213/inj.2014.18.4.187
    1. Sun J, Ke Z, Yip SP, Hu X, Zheng X, Tong K. Gradually increased training intensity benefits rehabilitation outcome after stroke by BDNF upregulation and stress suppression. Biomed Res Int. (2014) 2014:925762. 10.1155/2014/925762
    1. Ahn JH, Choi JH, Park JH, Kim IH, Cho JH, Lee JC, et al. . Long-term exercise improves memory deficits via restoration of myelin and microvessel damage, and enhancement of neurogenesis in the aged gerbil hippocampus after ischemic stroke. Neurorehab Neural Repair. (2016) 30:894–905. 10.1177/1545968316638444
    1. Himi N, Takahashi H, Okabe N, Nakamura E, Shiromoto T, Narita K, et al. . Exercise in the early stage after stroke enhances hippocampal brain-derived neurotrophic factor expression and memory function recovery. J Stroke Cerebrovasc Dis. (2016) 25:2987–94. 10.1016/j.jstrokecerebrovasdis.2016.08.017
    1. Takamatsu Y, Tamakoshi K, Waseda Y, Ishida K. Running exercise enhances motor functional recovery with inhibition of dendritic regression in the motor cortex after collagenase-induced intracerebral hemorrhage in rats. Behav Brain Res. (2016) 300:56–64. 10.1016/j.bbr.2015.12.003
    1. Yong MS, Hwangbo K. Skilled reach training influences brain recovery following intracerebral hemorrhage in rats. J Phys Ther Sci. (2014) 26:405–7. 10.1589/jpts.26.405
    1. Tamakoshi K, Kawanaka K, Onishi H, Takamatsu Y, Ishida K. Motor skills training improves sensorimotor dysfunction and increases microtubule-associated Protein 2 mRNA expression in rats with intracerebral hemorrhage. J Stroke Cerebrovasc Dis. (2016) 25:2071–7. 10.1016/j.jstrokecerebrovasdis.2016.05.007
    1. Ploughman M, Attwood Z, White N, Doré JJ, Corbett D. Endurance exercise facilitates relearning of forelimb motor skill after focal ischemia. Euro J Neurosci. (2007) 25:3453–60. 10.1111/j.1460-9568.2007.05591.x
    1. Yong MS, Kim SG, Cheon SH. Effects of skilled reach training with affected forelimb and treadmill exercise on the expression of neurotrophic factor following ischemia-induced brain injury in rats. J Phys Ther Sci. (2017) 29:647–650. 10.1589/jpts.29.647
    1. Hosp JA, Luft AR. Cortical plasticity during motor learning and recovery after ischemic stroke. Neural Plasticity (2011) 2011:871296. 10.1155/2011/871296
    1. Holleran CL, Rodriguez KS, Echauz A, Leech KA, Hornby TG. Potential contributions of training intensity on locomotor performance in individuals with chronic stroke. J Neurol Phys Ther. (2015) 39:95–102. 10.1097/NPT.0000000000000077
    1. Leddy AL, Connolly M, Holleran CL, Hennessy PW, Woodward J, Arena RA, et al. . Alterations in aerobic exercise performance and gait economy following high-intensity dynamic stepping training in persons with subacute stroke. J Neurol Phys Ther. (2016) 40:239–48. 10.1097/NPT.0000000000000147
    1. Ivey FM, Stookey AD, Hafer-Macko CE, Ryan AS, Macko RF. Higher Treadmill Training Intensity to Address Functional Aerobic Impairment after Stroke. J Stroke Cerebrovasc Dis. (2015) 24:2539–46. 10.1016/j.jstrokecerebrovasdis.2015.07.002
    1. Coelho FG, Gobbi S, Andreatto CA, Corazza DI, Pedroso RV, Santos-Galduróz RF. Physical exercise modulates peripheral levels of brain-derived neurotrophic factor (BDNF): a systematic review of experimental studies in the elderly. Arch Gerontol Geriatr. (2013) 56:10–15. 10.1016/j.archger.2012.06.003
    1. Ferris LT, Williams JS, Shen CL. The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function. Med Sci Sports Exerc. (2007) 39:728–34. 10.1249/mss.0b013e31802f04c7
    1. Huang T, Larsen KT, Ried-Larsen M, Møller NC, Andersen LB. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans: a review. Scand J Med Sci Sports (2014) 24:1–10. 10.1111/sms.12069
    1. Forti LN, Van Roie E, Njemini R, Coudyzer W, Beyer I, Delecluse C, et al. . Dose-and gender-specific effects of resistance training on circulating levels of brain derived neurotrophic factor (BDNF) in community-dwelling older adults. Exp Gerontol. (2015) 70:144–9. 10.1016/j.exger.2015.08.004
    1. Goekint M, De Pauw K, Roelands B, Njemini R, Bautmans I, Mets T, et al. Strength training does not influence serum brain-derived neurotrophic factor. Euro J Appl Physiol. (2010) 110:285–93. 10.1007/s00421-010-1461-3
    1. Roig M, Skriver K, Lundbye-Jensen J, Kiens B, Nielsen JB. A single bout of exercise improves motor memory. PLoS ONE (2012) 7:e44594. 10.1371/journal.pone.0044594
    1. Quaney BM, Boyd LA, McDowd JM, Zahner LH, He J, Mayo MS, et al. . Aerobic exercise improves cognition and motor function poststroke. Neurorehabit Neural Repair. (2009) 23:879–85. 10.1177/1545968309338193

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe