Dataset Information

Effects of Exercise Training on Neurotrophic Factors and Subsequent Neuroprotection in Persons with Multiple Sclerosis-A Systematic Review and Meta-Analysis.

ABSTRACT:

Background

Evidence indicates that exercise holds the potential to counteract neurodegeneration experienced by persons with multiple sclerosis (pwMS), which is in part believed to be mediated through increases in neurotrophic factors. There is a need to summarize the existing evidence on exercise-induced effects on neurotrophic factors alongside neuroprotection in pwMS.

Aim

To (1) systematically review the evidence on acute (one session) and/or chronic (several sessions) exercise-induced changes in neurotrophic factors in pwMS and (2) investigate the potential translational link between exercise-induced changes in neurotrophic factors and neuroprotection.

Methods

Five databases (Medline, Scopus, Web of Science, Embase, Sport Discus) were searched for randomized controlled trials (RCT) examining the effects of exercise (all modalities included) on neurotrophic factors as well as measures of neuroprotection if reported. The quality of the study designs and the exercise interventions were assessed by use of the validated tool TESTEX.

Results

From N = 337 identified studies, N = 14 RCTs were included. While only N = 2 of the identified studies reported on the acute changes in neurotrophic factors, all N = 14 RCTs reported on the chronic effects, with N = 9 studies revealing between-group differences in favor of exercise. This was most prominent for brain-derived neurotrophic factor (BDNF), with between-group differences in favor of exercise being observed in N = 6 out of N = 12 studies. Meta-analyses were applicable for three out of 10 different identified neurotrophic factors and revealed that exercise can improve the chronic levels of BDNF (delta changes; N = 9, ES = 0.78 (0.27; 1.28), p = 0.003, heterogeneity between studies) and potentially also ciliary neurotrophic factor (CNTF) (N = 3, ES = 0.24 (-0.07; 0.54), p = 0.13, no heterogeneity between studies) but not nerve growth factor (NGF) (N = 4, ES = 0.28 (-0.55; 1.11), p = 0.51, heterogeneity between studies). Indicators of neuroprotection (e.g., with direct measures of brain structure assessed by MRI) were assessed in N = 3 of the identified studies only, with N = 2 partly supporting and thus indicating a potential translational link between increases in neurotrophic factors and neuroprotection.

Conclusion

The present study reveals that exercise can elicit improvements in chronic levels of BDNF in pwMS, whereas the effects of exercise on chronic levels of other neurotrophic factors and on acute levels of neurotrophic factors in general, along with a potential translational link (i.e., with exercise-induced improvements in neurotropic factors being associated with or even mediating neuroprotection), are sparse and inconclusive. There is a need for more high-quality studies that assess neurotrophic factors (applying comparable methods of blood handling and analysis) concomitantly with neuroprotective outcome measures. Review Registration: PROSPERO (ID: CRD42020177353).

SUBMITTER: Diechmann MD

PROVIDER: S-EPMC8615767 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThere has been an exponential growth in the number of clinical research studies regarding exercise training in multiple sclerosis, and literature reviews and meta-analyses have documented the many benefits of exercise training. This research further requires careful review for documenting the safety of exercise training in multiple sclerosis, as clarity on safety represents a major hurdle in the clinical prescription of exercise behaviour.ObjectivesTo enhance understanding of the feasibility of exercise in multiple sclerosis, we (1) provide a protocol of a systematic review and meta-analysis that summarises rates and risks of clinical relapse, adverse events (i.e., an unfavourable outcome that occurs during the intervention delivery time period), and serious adverse events (i.e., an untoward occurrence that results in death or is life threatening, requires hospitalisation, or results in disability during the intervention delivery time period), as well as retention, adherence, and compliance, from randomised controlled trials of exercise training in persons with multiple sclerosis; and (2) identify moderators of relapse, adverse events, and serious adverse event rates.MethodsEight field-relevant databases will be searched electronically. Studies that involve a randomised controlled trial of exercise training (with non-exercise, non-pharmacological, comparator), report on safety outcomes, and include adults with multiple sclerosis will be included. Rates and relative risks of the three primary outcomes (relapse, adverse event, and serious adverse event) will be calculated and reported each with standard error and 95% confidence interval. Random-effects meta-analysis will estimate mean population relative risk for outcomes. Potential sources of variability, including participant characteristics, features of the exercise stimulus, and comparison condition, will be examined with random-effects meta-regression with maximum likelihood estimation.DiscussionThe results from this systematic review and meta-analysis will inform and guide healthcare practitioners, researchers, and policymakers on the safety of exercise training in persons with multiple sclerosis. Where possible, we will identify the impact of exercise type, exercise delivery style, participant disability level, and the prescription of exercise guidelines, on the safety of exercise training. The result will identify critical information on the safety of exercise in persons with multiple sclerosis, while also identifying gaps in research and setting priorities for future enquiries.Systematic review registrationPROSPERO 2020 CRD42020190544.

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