Skip to main content
NCBI home page
The Journal of Spinal Cord Medicine logoLink to The Journal of Spinal Cord Medicine
. 2020 Oct 15;45(3):455–460. doi: 10.1080/10790268.2020.1816402

Increased serum levels of brain-derived neurotrophic factor following wheelchair half marathon race in individuals with spinal cord injury

Yukihide Nishimura 1, Takeshi Nakamura 2, Yoshi-ichiro Kamijo 3, Hideki Arakawa 2, Yasunori Umemoto 3, Tokio Kinoshita 3, Yuta Sakurai 4, Fumihiro Tajima 3,✉
PMCID: PMC9135440  PMID: 33054672

Abstract

Objective: Brain-derived neurotrophic factor (BDNF) has beneficial effects on metabolism as well as the peripheral and central nervous systems. The aim of this study was to assess the response of serum BDNF concentration ([BDNF]s) to wheelchair half marathon race in individuals with spinal cord injury (SCI).

Design: Prospective observational study.

Setting: The 34th Oita International Wheelchair Marathon Race in Japan.

Participants: Nine cervical SCIs (CSCI) and 8 thoracic and lumber SCIs (LSCI) male athletes. Interventions: Wheelchair half-Marathon Race.

Outcome measures: [BDNF]s, plasma concentrations of adrenaline ([Ad]p), noradrenaline ([Nor]p), and cortisol ([Cor]p), hematocrit, and platelet count were measured the day before, immediately after, and an hour after the race.

Results: [BDNF]s increased significantly immediately after the race in both groups (CSCI; P = 0.0055, LSCI; P = 0.0312) but returned to the baseline levels at one hour after the race. However, [BDNF]s immediately and one hour after the race were significantly higher in LSCI than in CSCI (immediately after the race; P = 0.0037, 1 h after the race; P = 0.0206). Hematocrit and platelet count remained unchanged throughout the study. In LSCI, [Ad]p, [Nor]p and [Cor]p increased significantly immediately after and one hour after the race, compared with the baseline values (P < 0.05). On the other hand, these variables remained unchanged throughout the study in the CSCI.

Conclusions: [BDNF]s increased significantly from the baseline in both LCSI and CSCI but was higher in LSCI than in CSCI immediately after and one hour after the race.

Keywords: Wheelchair sports, Health promotion, Exercise, BDNF

Introduction

Brain-derived neurotrophic factor (BDNF) regulates various neurotrophic functions, including neuroregeneration, neuroprotection, and synaptic plasticity,1 and stimulates neuronal survival in the peripheral and central nervous systems.2 In addition, BDNF has several beneficial effects and is known to reduce food intake, increase glucose oxidation and insulin sensitivity,3,4 and enhance fat oxidation.5 The concentrations of BDNF in the brain and peripheral circulation are lower in patients with Alzheimer’s disease and those with major neurodegenerative diseases,6–8 and also in patients with type 2 diabetes.9 On the other hand, acute and chronic aerobic exercise, and strength training are known to increase peripheral BDNF levels.10 Taken together, the above studies highlight the overall beneficial effects of BDNF on health.

Many of individuals with spinal cord injury (SCI) use a wheelchair for mobility due to the associated motor dysfunction.11 The daily energy expenditure tends to be lower in such individuals using a manual wheelchair than able-bodied (AB) persons.12 It is well known that heart disease and type 2 diabetes are more common in persons with SCI than AB persons,13 and thus the importance of exercise and/or sports activities needs to be emphasized in SCI individuals, as in AB14 in order to prevent the abovementioned complications.

Nowadays, individuals with SCI can enjoy various sports thanks to improvement in medical management and rehabilitation.15 However, the percentage of SCI individuals participating in such activities is low in Japan (<20%).16 A recent longitudinal study over 20-year period has demonstrated that the maximum oxygen consumption (VO2max) of athletes with SCI who had participated in wheelchair marathon races was maintained or increased.17 Thus, participation in wheelchair marathon and/or training to participate in this sport event would be positively associated with the maintenance or improvement of physical fitness, in part due to high levels of serum BDNF in each exercise or sports activity.

Only two previous studies have so far analyzed serum concentration of BDNF ([BDNF]s) in response to acute bouts of exercise in individuals with SCI. Rojas-Vega et al.18 reported that 10-min moderate exercise at 54% of VO2max significantly increased [BDNF]s. On the other hand, Zeller et al.19 reported that a typical training session does not affect basal [BDNF]s in wheelchair rugby athletes with cervical SCI (CSCI). These studies point to no clear association between a bout of exercise and [BDNF]s in this population. Moreover, the physiological features of individuals with CSCI are quite different from those of subjects with lower SCI (LSCI), especially because individuals with CSCI have limited available muscles on the upper limbs compared with LSCI and muscle atrophy in the whole body is also severer in CSCI than LSCI.

The purpose of this study was to determine whether participation in a wheelchair half-marathon race is associated with an increase in [BDNF]s in two groups of athletes, those with CSCI and LSCI. We also analyzed the simultaneous changes in plasma concentrations of catecholamine and cortisol.

Methods

Participants

Nine CSCI and 8 LSCI athletes provided informed consent and voluntarily participated in the study. All participants completed the half-marathon race the 34th Oita International Wheelchair Marathon Race in Japan and had been involved in regular physical training programs before the race. The inclusion criteria included: (1) males; this is a convenience sample of athletes at this marathon, not highly attended by women, therefore recruitment of an adequate sample size of women was not possible, (2) lack of neurological changes more than one year after the initial injury, (3) International Standards for Classification of Spinal Cord Injury American Spinal Injury Association Impairment Scale A, i.e., representing complete SCI, (4) lack of clinically-evident acute infection and in good general health except for SCI-related dysfunctions, and (5) not on any medications that would affect cardiovascular or endocrine responses during the study period. The study protocol was approved by the ethics committee Wakayama Medical University and conformed to the Declaration of Helsinki.

Study protocol

Blood samples were taken from the antecubital vein in the afternoon of the day before the race after the athletes checked in the reception desk. Furthermore, second and third samples were taken immediately after and an hour after the race. Each blood sample was divided into 2, 5, and 6 mL and placed into 2K+ for blood cell counts, a vacutainer containing ethylenediaminetetraacetic acid-2Na+ for assays of plasma concentrations of adrenaline ([Ad]p), noradrenaline ([Nor]p), and cortisol ([Cor]p) and serum separator tubes for [BDNF]s, respectively. The collecting tubes were spun immediately at 3500 rpm for 10 min at 4°C and the obtained plasma and serum samples were stored at −80°C until assays.

Blood analyses

BDNF was measured by enzyme-linked immunosorbent assay (ELISA) for BDNF (DBD00, R&D Systems, Minneapolis, MN) with assay sensitivity <20 pg/ml and intra- and inter-assay coefficients of variability (average CV of different concentrations) of 5.0 and 9.0%, respectively. All measurements were performed in duplicates.

Hematocrit was determined and total blood cell counts, including platelet count, was determined using a cell counter (MEK-6400, Nihon Koden, Tokyo). Catecholamines were extracted from plasma with alumina and measured by high-performance liquid chromatography using a modification of the procedure described by Hunter et al.20 Plasma cortisol levels were measured using a competitive solid phase125 I radioimmunoassay technique (Dainabot Lab, Tokyo, Japan).

Statistical analysis

Data were expressed as mean ± standard error of the mean (SEM). All data were tested by two-way analysis of variance (ANOVA) for repeated measurements. Subsequent post-hoc tests to determine significant differences were performed by Tukey-Kramer test. If necessary, simple linear regression analysis was adopted to analyze the relationship between [BDNF]s and some. These statistical evaluations were performed using Graph Pad Prism 6 software (GraphPad Software Inc, San Diego, CA).

Means of [BDNF]s just after the race were 22379 and 30600 pg/mL and SDs of 3790 and 4164 pg/mL with a sample size of 9 and 8 in CSCI and LSCI, respectively. If α would be assumed as 0.05, then a statistical power was 0.98 (G*Power Version 3.1.9.6 written by Franz Faul in Univ. Kiel, Germany).

Results

Table 1 summarizes the anthropometric and laboratory findings. The injury levels of the CSCI subjects were at C5 (n = 2), C6 (n = 3), C7 (n = 3) and C8 (n = 1), while that of the LSCI group were at Th8 (n = 1), Th11 (n = 3), Th12 (n = 3) and L1 (n = 1). Subjects of the LSCI athletes were older than those of the CSCI (P = 0.004) and the time since injury was longer in LSCI participants (P = 0.0098). Height, body weight, and body mass index were similar between the two groups. The mean race time for the half-marathon race was 1’02; 30 and 1’26; 43 for the LSCI and CSCI athletes, respectively.

Table 1. Anthropometric data of the participating athletes.

  LSCI group CSCI group P value
Number 8 9  
Age (years) 56 ± 4 35 ± 4 0.0040
Height (cm) 169.9 ± 1.4 173.0 ± 2.5 0.3386
Weight (kg) 62.6 ± 2.1 56.2 ± 3.7 0.1899
Body mass index (kg/m2) 21.7 ± 0.8 18.8 ± 1.1 0.0568
Spinal lesion T8-L1 C5-C8  
Time since injury (months) 381 ± 63 161 ± 35 0.0098
Open in a new tab

Data are mean ± SEM.

LSCI, Athletes with low spinal cord injury; CSCI, Athletes with cervical spinal cord injury.

There was no significant difference in [BDNF]s before the race (baseline) between the groups. [BDNF]s significantly increased immediately after the race in both groups (CSCI, P = 0.0055; LSCI, P = 0.0312) and returned to the baseline level an hour after the race. Furthermore, [BDNF]s immediately and an hour after the race were significantly higher in the LSCI group compared with the CSCI group (P = 0.0037, P = 0.0206, respectively, Fig. 1).

Figure 1.

Figure 1

Open in a new tab

Serum BDNF levels. Data are mean ± SEM. *P < 0.05, between the LSCI and CSCI groups. #P < 0.05, compared with the pre-race values. ##P < 0.05, compared with the post-race values. BDNF, brain derived neurotrophic factor; LSCI, Athletes with low spinal cord injury; CSCI, Athletes with cervical spinal cord injury.

The platelet count and hematocrit remained stable throughout the study and there were no differences between the two groups (Fig. 2). In the LSCI group, [Ad]p. [Nor]p, and [Cor]p significantly increased immediately after the race (P < 0.0001, P < 0.0001, and P = 0.0079, respectively) and also an hour after the race compared with the baseline (P = 0.0033, P = 0.0218, and P = 0.0036, respectively). However, the above plasma concentrations did not change throughout the study in CSCI participants (Fig. 2). There were no significant correlations between changes in [BDNF]s and [Ad]p (r = −0.0230; P = 0.9569), [Nor]p (r = −0.0959; P = 0.8214), or [Cor]p from baseline (r = −0.1694; P = 0.6883) in the LCSI group.

Figure 2.

Figure 2

Open in a new tab

Platelet count (A) and serum levels of adrenaline (B), noradrenaline (C) and cortisol (D). Data are mean ± SEM. *P < 0.05, between the LSCI and CSCI groups. #P < 0.05, compared with the pre-race values. ##P < 0.05, compared with the post-race values. Abbreviations as in Figure 1.

Discussion

The following were the major findings of the present study; (1) [BDNF]s increased in both groups after the race, but (2) was higher in the LSCI group than that in the CSCI group immediately after the race, (3) [Ad]p, [Nor]p, and [Cor]p increased after the race only in the LSCI group, and (4) platelet count and hematocrit remained unchanged throughout the race in both groups.

Previous studies have reported that acute aerobic exercise is associated with a significant increase in [BDNF]s but the concentration returns to the baseline soon after exercise.21–25 Both the intensity and duration of aerobic exercise seem to influence the magnitude of increase in [BDNF]s. For example, in healthy individuals, [BDNF]s increased after 30-min bicycle ergometry at 60% of VO2max [21] and 15-min moderate step exercise25 but the levels returned to the baseline level within 30 min after the exercise.18 In the SCI population, moderate intensity hand-ergometer exercise at 54% of the maximal heart rate during the warm-up period induced approximately 1.5-fold increase in BDNF, relative to the baseline level (P < 0.05), but a decrease to the baseline was found immediately after a hand-ergometer time trial (89% of the maximal heart rate) for ∼85 min.18 Furthermore, the typical wheelchair rugby training session did not affect [BDNF]s at baseline in elite athletes with CSCI.19 Although the reason for the discrepancy is unknown, the intensity and race duration of a wheelchair half marathon were sufficient to increase in [BDNF]s in the population of the present study.

One of the reasons for the higher [BDNF]s after the race in LSCI may be related to the mass of available muscles. The higher mass released the more myokines such as irisin and cathepsin B, which is capable of crossing the blood–brain barrier to induce BDNF.26 Several animal studies reported that BDNF mRNA increases in contracting skeletal muscles.5,27,28 Even BDNF increases within contracting skeletal muscle tissues in humans, it does not seem to release into the circulation.5 In general, the higher the injury level of SCI, the more profound motor paresis is below the level of the injury. Therefore, the mass of contracting muscles during wheelchair propulsion is less in individuals with CSCI than in LSCI. Furthermore, it has been reported that CSCI individuals with long-standing injury have strikingly low muscle fiber area below the level of injury.29 In other words, muscles of the trunk and lower extremities did not contract during the race in the present CSCI athletes, whereas the contracting muscles during the race in LSCI athletes included not only those of the upper extremities but also the trunk. Therefore, the difference in [BDNF]s in this race between the groups could reflect the difference in the mass of active muscles during the race.

A second explanation could be explained by the level of impairment of the sympathetic nervous system, because BDNF develops sympathetic nervous system and regulates sympathetic transmitter expression.30 However, in the present study, as the level of [Ad]p remained stable throughout the study in the CSCI athletes, consisting with the previous studies in CSCI.31–33 In this regard, Goekint et al.24 reported that administration of a selective noradrenaline reuptake inhibitor had no effect on exercise-induced increase in [BDNF]s. Thus, contributions of catecholamines to the release of BDNF was quietly low.

Cortisol and BDNF complement the actions of each other in the nervous system.34 Physical stress, such as exercise, increases plasma cortisol levels and the basal levels are higher also in neuropsychiatric disorders. Mental stress in neuropsychiatric disorders is associated with hypercortisolemia and inhibits the expression of BDNF in the brain and its release into the peripheral circulation.34–36 Thus, the exercise-induced increase in [Cor]p likely inhibits the expression or release of BDNF. Indeed, [BDNF]s and [Cor]p after the race were significantly higher in LCSI than in CSCI and the patterns of responses were similar between the groups in the present study. However, the increase in [BDNF]s was not correlated with that of [Cor]p in the present study. Furthermore, one previous study showed a faster return of [BDNF]s to the baseline level after a bout of exercise, compared with cortisol.22 Therefore, the increase in [BDNF]s did not seem to be related to cortisol response.

Most of the BDNF in the blood is stored in the platelets.25,37,38 Moreover, [BDNF]s correlates with platelet count at rest in smokers and non-smokers39 as well as in obese individuals from early childhood to adolescence.40 The exercise-induced increase in [BDNF]s seems to originate from the platelets.24,41 However, in the present study, the [BDNF]s response pattern was inconsistent with that of platelet count in both groups of subjects. These findings suggest that aerobic activity in the present study seems to stimulate BDNF production from other body tissues rather than the platelets.

Our results also showed no change in hematocrit level throughout the study, probably because the subjects were allowed to eat and drink freely before and during the race. This finding suggests that the race did not induce hemoconcentration in both groups and that hemoconcentration was not a factor in the observed increase in [BDNF]s.

Our study has certain limitations. These include the small sample size and the lack of analysis of the effect of age on the recorded variables. Previous studies reported the presence of low plasma BDNF levels in older adults compared with younger individuals.42–44 Although age was different between the groups in the present study, we could not evaluate the potential effect of age on the tested variables. However, the influences of aging would be strong in much older population (>70s).43,44 Also, the time since injury was significantly different between the two groups. To our knowledge, there is no information in the literature on the effect of time since SCI on BDNF level.

Conclusions

We demonstrated in the present study an increase in [BDNF]s in both LCSI and CSCI athletes occurring immediately after a wheelchair half marathon race. Furthermore, the level of [BDNF]s was significantly higher in LSCI than in CSCI athletes. The results suggest that strenuous aerobic exercise, such as wheelchair half marathon, has beneficial health effects in individuals with SCI. In the future, a prospective study is anticipated to perform whether persons who have greater response of BDNF after each exercise session achieve more beneficial effects during a period of aerobic training.

Acknowledgments

We thank Dr. Faiq G. Issa (www.word-medex.com.au) for the careful reading and editing of the manuscript.

Disclaimer statements

Contributors None.

Funding None.

Conflicts of interest Authors have no conflict of interests to declare.

References

  • 1.Huang EJ, Reichardt LF.. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 2001;24:677–736. doi: 10.1146/annurev.neuro.24.1.677 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Ritfeld GJ, Patel A, Chou A, Novosat TL, Castillo DG, Roos RA, et al. The role of brain-derived neurotrophic factor in bone marrow stromal cell-mediated spinal cord repair. Cell Transplant 2015;24(11):2209–20. doi: 10.3727/096368915X686201 [DOI] [PubMed] [Google Scholar]
  • 3.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(9):765–801. doi: 10.2165/11534530-000000000-00000 [DOI] [PubMed] [Google Scholar]
  • 4.Ono M, Ichihara J, Nonomura T, Itakura Y, Taiji M, Nakayama C, et al. Brain-derived neurotrophic factor reduces blood glucose level in obese diabetic mice but not in normal mice. Biochem Biophys Res Commun 1997;238(2):633–7. doi: 10.1006/bbrc.1997.7220 [DOI] [PubMed] [Google Scholar]
  • 5.Matthews VB, Aström MB, Chan MH, Bruce CR, Krabbe KS, Prelovsek O, et al. 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. Diabetologia 2009;52(7):1409–18. doi: 10.1007/s00125-009-1364-1 [DOI] [PubMed] [Google Scholar]
  • 6.Phillips HS, Hains JM, Armanini M, Laramee GR, Johnson SA, Winslow JW.. BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer’s disease. Neuron 1991;7(5):695–702. doi: 10.1016/0896-6273(91)90273-3 [DOI] [PubMed] [Google Scholar]
  • 7.Karege F, Vaudan G, Schwald M, Perroud N, La Harpe R.. Neurotrophin levels in postmortem brains of suicide victims and the effect of antemortem diagnosis and psychotropic drugs. Mol Brain Res 2005;136(1-2):29–37. doi: 10.1016/j.molbrainres.2004.12.020 [DOI] [PubMed] [Google Scholar]
  • 8.Laske C, Stransky E, Leyhe T, Eschweiler GW, Wittorf A, Richartz E, et al. Stage-dependent BDNF serum concentrations in Alzheimer’s disease. J Neural Transm 2006;113(9):1217–24. doi: 10.1007/s00702-005-0397-y [DOI] [PubMed] [Google Scholar]
  • 9.Zhen YF, Liu XY, Li YK, Fang H, Cassidy RM, Zhang XY.. Association of brain-derived neurotrophic factor with cognitive function: an investigation of sex differences in patients with type 2 diabetes. Psychosom Med 2019;81(6):488–94. doi: 10.1097/PSY.0000000000000709 [DOI] [PubMed] [Google Scholar]
  • 10.Kawazu T, Nakamura T, Moriki T, Kamijo YI, Nishimura Y, Kinoshita T, et al. Aerobic exercise combined with noninvasive positive pressure ventilation increases serum brain-derived neurotrophic factor in healthy males. PM R 2016;8(12):1136–41. doi: 10.1016/j.pmrj.2016.05.004 [DOI] [PubMed] [Google Scholar]
  • 11.Post MW, van Asbeck FW, van Dijk AJ, Schrijvers AJ.. Services for spinal cord injured: availability and satisfaction. Spinal Cord 1997;35(2):109–15. doi: 10.1038/sj.sc.3100362 [DOI] [PubMed] [Google Scholar]
  • 12.Monroe MB, Tataranni PA, Pratley R, Manore MM, Skinner JS, Ravussin E.. Lower daily energy expenditure as measured by a respiratory chamber in subjects with spinal cord injury compared with control subjects. Am J Clin Nutr 1998;68(6):1223–7. doi: 10.1093/ajcn/68.6.1223 [DOI] [PubMed] [Google Scholar]
  • 13.Bauman WA, Spungen AM.. Coronary heart disease in individuals with spinal cord injury: assessment of risk factors. Spinal Cord 2008;46(7):466–76. doi: 10.1038/sj.sc.3102161 [DOI] [PubMed] [Google Scholar]
  • 14.Petersen AM, Pedersen BK.. The anti-inflammatory effect of exercise. J Appl Physiol 2005;98(4):1154–62. doi: 10.1152/japplphysiol.00164.2004 [DOI] [PubMed] [Google Scholar]
  • 15.Sasagawa Sports Foundation . A report of sports environments for persons with impairments in foreign countries: United Kingdom, Canada, and Australia (In Japanese). 2017. Available from http://www.ssf.or.jp/research/report/category5/tabid/1433/Default.aspx.
  • 16.Japan Sports Agency . The sport basic plan in the second stage (In Japanese). 2017.
  • 17.Shiba S, Okawa H, Uenishi H, Koike Y, Yamauchi K, Asayama K, et al. Longitudinal changes in physical capacity over 20 years in athletes with spinal cord injury. Arch Phys Med Rehabil 2010;91(8):1262–6. doi: 10.1016/j.apmr.2010.04.024 [DOI] [PubMed] [Google Scholar]
  • 18.Rojas Vega S, Abel T, Lindschulten R, Hollmann W, Bloch W, Strüder HK.. Impact of exercise on neuroplasticity-related proteins in spinal cord injured humans. Neuroscience 2008;153(4):1064–70. doi: 10.1016/j.neuroscience.2008.03.037 [DOI] [PubMed] [Google Scholar]
  • 19.Zeller S, Abel T, Rojas-Vega S, Foitschik T, Strueder HK.. Brain-derived neurotrophic factor concentrations in tetraplegic athletes. Spinal Cord 2015;53(11):791–4. doi: 10.1038/sc.2015.94 [DOI] [PubMed] [Google Scholar]
  • 20.Hunter LW, Rorie DK, Yaksh TL, Tyce GM.. Concurrent separation of catecholamines, dihydroxyphenylglycol, vasoactive intestinal peptide, and neuropeptide Y in superfusate and tissue extract. Anal Biochem 1988;173(2):340–52. doi: 10.1016/0003-2697(88)90198-4 [DOI] [PubMed] [Google Scholar]
  • 21.Gold SM, Schulz KH, Hartmann S, Mladek M, Lang UE, Hellweg R, et al. Basal serum levels and reactivity of nerve growth factor and brain-derived neurotrophic factor to standardized acute exercise in multiple sclerosis and controls. J Neuroimmunol 2003;138(1-2):99–105. doi: 10.1016/S0165-5728(03)00121-8 [DOI] [PubMed] [Google Scholar]
  • 22.Rojas Vega S, Struder HK, Vera Wahrmann B, Schmidt A, Bloch W, Hollman W.. Acute BDNF and cortisol response to low intensity exercise and following ramp incremental exercise to exhaustion in humans. Brain Res 2006;1121(1):59–65. doi: 10.1016/j.brainres.2006.08.105 [DOI] [PubMed] [Google Scholar]
  • 23.Dinoff A, Herrmann N, Swardfager W, Lanctôt KL.. The effect of acute exercise on blood concentrations of brain-derived neurotrophic factor in healthy adults: a meta-analysis. Eur J Neurosci 2017;46(1):1635–46. doi: 10.1111/ejn.13603 [DOI] [PubMed] [Google Scholar]
  • 24.Goekint M, Heyman E, Roelands B, Njemini R, Bautmans I, Mets T, et al. No influence of noradrenaline manipulation on acute exercise-induced increase of brain-derived neurotrophic factor. Med Sci Sports Exerc 2008;40(11):1990–6. doi: 10.1249/MSS.0b013e31817eee85 [DOI] [PubMed] [Google Scholar]
  • 25.Tang SW, Chu E, Hui T, Helmeste D, Law C.. Influence of exercise on serum brain-derived neurotrophic factor concentrations in healthy human subjects. Neurosci Lett 2008;431(1):62–5. doi: 10.1016/j.neulet.2007.11.019 [DOI] [PubMed] [Google Scholar]
  • 26.Moon HY, Becke A, Berron D, Becker B, Sah N, Benoni G, et al. Running-induced systemic cathepsin B secretion is associated with memory function. Cell Metab 2016;24(2):332–40. doi: 10.1016/j.cmet.2016.05.025 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Dupont-Versteegden EE, Houlé JD, Dennis RA, Zhang J, Knox M, Wagoner G, et al. Exercise-induced gene expression in soleus muscle is dependent on time after spinal cord injury in rats. Muscle Nerve 2004;29(1):73–81. doi: 10.1002/mus.10511 [DOI] [PubMed] [Google Scholar]
  • 28.Gómez-Pinilla F, Ying Z, Opazo P, Roy RR, Edgerton VR.. Differential regulation by exercise of BDNF and NT-3 in rat spinal cord and skeletal muscle. Eur J Neurosci 2001;13(6):1078–84. doi: 10.1046/j.0953-816x.2001.01484.x [DOI] [PubMed] [Google Scholar]
  • 29.Aksnes AK, Hjeltnes N, Wahlstrom EO, Katz A, Zierath JR, Wallberg-Henriksson H.. Intact glucose transport in morphologically altered denervated skeletal muscle from quadriplegic patients. Am J Physiol 1996;271:E593–600. [DOI] [PubMed] [Google Scholar]
  • 30.Luther JA, Birren SJ.. Neurotrophins and target interactions in the development and regulation of sympathetic neuron electrical and synaptic properties. Auton Neurosci 2009;151(1):46–60. doi: 10.1016/j.autneu.2009.08.009 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Mitsui T, Ito T, Sasaki Y, Kawasaki T, Nakamura T, Nishimura Y, et al. Changes in oxidized LDL during a half marathon in athletes with spinal cord injuries. Spinal Cord Ser Cases 2017;3:17015. doi: 10.1038/scsandc.2017.15.eCollection2017. doi: [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Ogawa T, Nakamura T, Banno M, Sasaki Y, Umemoto Y, Kouda K, et al. Elevation of interleukin-6 and attenuation of tumor necrosis factor-α during wheelchair half marathon in athletes with cervical spinal cord injuries. Spinal Cord 2014;52(8):601–5. doi: 10.1038/sc.2014.88 [DOI] [PubMed] [Google Scholar]
  • 33.Umemoto Y, Furusawa K, Kouda K, Sasaki Y, Kanno N, Kojima D, et al. Plasma IL-6 levels during arm exercise in persons with spinal cord injury. Spinal Cord 2011;49(12):1182–7. doi: 10.1038/sc.2011.74 [DOI] [PubMed] [Google Scholar]
  • 34.de Assis GG, Gasanov EV.. BDNF and cortisol integrative system - plasticity vs. degeneration: implications of the Val66Met polymorphism. Front Neuroendocrinol 2019;55:100784. doi: 10.1016/j.yfrne.2019.100784. Epub 2019 Aug 16. [DOI] [PubMed] [Google Scholar]
  • 35.Murakami S, Imbe H, Morikawa Y, Kubo C, Senba E.. Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly. Neurosci Res 2005;53(2):129–39. doi: 10.1016/j.neures.2005.06.008 [DOI] [PubMed] [Google Scholar]
  • 36.Naveen GH, Varambally S, Thirthalli J, Rao M, Christopher R, Gangadhar BN.. Serum cortisol and BDNF in patients with major depression-effect of yoga. Int Rev Psychiatry 2016;28(3):273–8. doi: 10.1080/09540261.2016.1175419 [DOI] [PubMed] [Google Scholar]
  • 37.Huang T, Larsen KT, Ried-Larsen M, Moller 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):1–10. doi: 10.1111/sms.12069 [DOI] [PubMed] [Google Scholar]
  • 38.Nakahashi T, Fujimura H, Altar CA, Li J, Kambayashi J, Tandon NN, et al. Vascular endothelial cells synthesize and secrete brain-derived neurotrophic factor. FEBS Lett 2000;470(2):113–7. doi: 10.1016/S0014-5793(00)01302-8 [DOI] [PubMed] [Google Scholar]
  • 39.Suriyaprom K, Tungtrongchitr R, Thawnashom K, Pimainog Y.. BDNF Val66Met polymorphism and serum concentrations of BDNF with smoking in Thai males. Genet Mol Res 2013;12(4):4925–33. doi: 10.4238/2013.October.24.3 [DOI] [PubMed] [Google Scholar]
  • 40.El-Gharbawy AH, Adler-Wailes DC, Mirch MC, Theim KR, Ranzenhofer L, Tanofsky-Kraff M, et al. Serum brain-derived neurotrophic factor concentrations in lean and overweight children and adolescents. J Clin Endocrinol Metab 2006;91(9):3548–52. doi: 10.1210/jc.2006-0658 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Cho HC, Kim J, Kim S, Son YH, Lee N, Jung SH.. The concentrations of serum, plasma and platelet BDNF are all increased by treadmill VO2max performance in healthy college men. Neurosci Lett 2012;519(1):78–83. doi: 10.1016/j.neulet.2012.05.025 [DOI] [PubMed] [Google Scholar]
  • 42.Lommatzsch M, Zingler D, Schuhbaeck K, Schloetcke K, Zingler C, Schuff-Werner P, et al. The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging 2005;26(1):115–23. doi: 10.1016/j.neurobiolaging.2004.03.002 [DOI] [PubMed] [Google Scholar]
  • 43.Shimada H, Makizako H, Doi T, Yoshida D, Tsutsumimoto K, Anan Y, et al. A large, cross-sectional observational study of serum BDNF, cognitive function, and mild cognitive impairment in the elderly. Front Aging Neurosci 2014;6:69. doi: 10.3389/fnagi.2014.00069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Walsh EI, Smith L, Northey J, Rattray B, Cherbuin N.. Towards an understanding of the physical activity-BDNF-cognition triumvirate: a review of associations and dosage. Ageing Res Rev 2020;60:101044. doi: 10.1016/j.arr.2020.101044 [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Spinal Cord Medicine are provided here courtesy of Taylor & Francis

RESOURCES