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

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

Carolina C. Alcantara¹, Luisa F. García-Salazar^1,2, Marcela A. Silva-Couto¹, Gabriela L. Santos¹, Darcy S. Reisman³ and Thiago L. Russo^1*

• ¹Laboratory of Neurological Physiotherapy Research, Physical Therapy Department, Federal University of São Carlos, São Carlos, Brazil
• ²Escuela de Medicina y Ciencias de la Salud, GI Ciencias de la Rehabilitación, Universidad del Rosario, Bogotá, Colombia
• ³Department of Physical Therapy, University of Delaware, Newark, DE, United States

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.

Introduction

Research over the last 10 years has demonstrated that Brain-derived neurotrophic factor (BDNF) plays an important role in brain plasticity in the intact brain (1, 2), as well as after central nervous system (CNS) damage (3, 4). BDNF is a member of the neurotrophin family, known for its role in neuronal proliferation, survival and differentiation (1). Along with its receptor tyrosine kinase, this neurotrophin is largely distributed throughout the healthy human brain (5, 6).

The role of BDNF after stroke has been highlighted in many studies (3, 4, 7–10). Its action is related not only to the induction of anti-apoptotic mechanisms, reducing the size of the lesion, but also to secondary neuronal death (3) Furthermore, motor learning post-stroke has been related to increases in BDNF concentrations in the cortex (10), which may accomplish cortical map reorganization through synaptogenesis, enhanced dendritic spine formation and ramification, thereby contributing in many ways to neuronal plasticity post-stroke (3, 4, 9).

Given the evidence linking BDNF and brain plasticity, research advancements have been made aiming to understand the response of BDNF levels to physical exercise training and how these changes would mediate the beneficial effects of exercise on learning (8, 11, 12). This systematic review specifically emphasized studies that examined exercise intervention, not exercise as a priming (e.g.,-single session, before and after exercise measurements only). Converging results available in the literature suggest that aerobic exercise training may lead to an increase in BDNF concentrations in neurologically intact humans (13). Thus, using aerobic training as an intervention to optimize neuroplasticity and recovery in patients post-stroke has gained considerable interest (10). Although there is still a lack of studies evaluating BDNF concentrations following exercise in subjects post-stroke, evidence based on stroke-induced animal models suggests a relationship between aerobic exercise training and an increase in BDNF concentrations (14–16) Furthermore, recent studies have also measured BDNF concentrations following functional task training in stroke-induced animals models, such as skilled reach training, in order to further clarify the mechanisms by which these interventions would induce recovery (17, 18).

However, given the controversial results between studies, the relationship between exercise training (aerobic and/or functional task training) and BDNF levels post-stroke has not been fully elucidated. Although previous literature reviews have addressed the effects of aerobic exercise on neuroplasticity in general after stroke (7, 8) the focus of the current review is on the role of BDNF in the physical exercise response, either aerobic and/or functional task training, in human or animal models of stroke. Thus, the primary objective of this study was to carry out a systematic review of literature investigating the effects of aerobic exercise and functional task training on BDNF concentrations in animals or humans post-stroke. The secondary objective of this review was to analyze the methodological quality of selected studies.