Investigating the Effect of Cardiovascular Exercise on Brain-Derived Neurotrophic Factor in Early Subacute Stroke

Abstract Background. Following stroke, a growth-promoting response resulting in heightened neuroplasticity occurs during the early subacute stages of recovery, a period during which the brain may be more responsive to therapeutical interventions. Given its central role in regulating neuroplastic processes and brain repair in animal models, brain-derived neurotrophic factor (BDNF) has been investigated as a potential biomarker for stroke recovery in humans, with interventions upregulating it holding therapeutical potential. Cardiovascular exercise (CE) has been recommended for stroke rehabilitation, partly due to its potential to induce neural adaptations, including upregulation of BDNF. Objectives. To examine the effects of CE on BDNF in individuals at early subacute stages of recovery. Methods. 76 participants within 3 months of first-ever ischemic stroke were randomly assigned to eight weeks of either CE plus standard care or standard care alone. To measure the chronic and acute responses to exercise in serum BDNF levels, blood samples were collected before and immediately after a graded exercise test conducted at baseline, four and eight weeks. The potential role of the BDNF Val66Met polymorphism in modulating the BDNF response to CE was also explored. Results. Despite significant increases in cardiorespiratory fitness, CE did not induce any significant chronic or acute changes in BDNF concentration. Similarly, the BDNF response to CE was not modulated by the Val66Met polymorphism or associated with changes in cardiorespiratory fitness and clinical outcomes. Conclusions. These findings indicate limited effects of CE in modulating circulating BDNF in subacute stages of stroke recovery. Trial Registration: Exercise and Genotype in Sub-acute Stroke: https://clinicaltrials.gov/study/NCT05076747