Investigating the Acute and Chronic Effects of Cardiovascular Exercise on Brain-Derived Neurotrophic Factor in Early Subacute Stroke

BackgroundFollowing 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 targeted as a potential biomarker for stroke recovery in humans, with interventions upregulating BDNF 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.ObjectivesTo examine the effects of CE on BDNF in individuals at early subacute stages of recovery.MethodsSeventy-six participants within 3 months of first-ever ischemic stroke were randomly assigned to 8 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, 4, and 8 weeks. The potential role of the BDNF Val66Met polymorphism in modulating the BDNF response was also explored. Data were analyzed following an intention-to-treat approach.ResultsDespite clinically important increases in cardiorespiratory fitness, CE did not induce significant chronic or acute changes in serum BDNF. Furthermore, the response to CE was not associated with changes in cardiorespiratory fitness and clinical outcomes or was modulated by Val66Met.ConclusionsThese findings indicate that CE has a limited capacity to upregulate circulating BDNF in subacute stages of stroke recovery.Trial Registration:Exercise and Genotype in Sub-acute Stroke: https://clinicaltrials.gov/study/NCT05076747.