BRIEF RESEARCH REPORT article
Front. Stroke
Sec. Stroke Recovery and Rehabilitation
Serum BDNF in Subacute Stroke: Effects of a Four-Week Aerobic Exercise Intervention in the PHYS-STROKE trial
- TR
Torsten Rackoll 1,2
- LD
Lea Doppelbauer 2
- KN
Konrad Neumann 2
- AH
Alexander Heinrich Nave 2
1. Berlin Institute of Health, Charité Medical University of Berlin, Berlin, Germany
2. Charite - Universitatsmedizin Berlin, Berlin, Germany
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Abstract
Introduction: The early phase after stroke is considered a period of heightened neuroplasticity and may be responsive to rehabilitation interventions targeting biological recovery. Brainderived neurotrophic factor is one candidate mediator of post-stroke plasticity, but it remains unclear whether clinically feasible aerobic exercise induces sustained increases in circulating brain-derived neurotrophic factor after stroke. Methods: We performed a pre-specified secondary biomarker analysis of the multicentre, randomized, endpoint-blinded Physical Fitness Training in Patients with Subacute Stroke trial. Participants were randomized to four weeks of moderate-intensity treadmill-based aerobic training or relaxation therapy. Serum brain-derived neurotrophic factor was assessed from baseline to six months post-stroke. Models were adjusted for baseline brain-derived neurotrophic factor, age, sex, stroke severity, platelet count, depressive symptoms, smoking status, and study centre. Results: Among 200 randomized participants, serum brain-derived neurotrophic factor increased modestly from baseline to three months and remained stable thereafter. No relevant between-group difference was observed at six months after aerobic training compared with relaxation therapy (training: 24.6 ng/mL; 95% CI, 20.2–29.0 vs relaxation: 24.3 ng/mL; 95% CI, 19.8–28.8; adjusted p = 0.74). Findings were consistent in complete-case and changescore sensitivity analyses. Exploratory analyses showed no robust treatment effect modification by depressive symptoms or intervention dose. A nominal sex-related subgroup finding should be interpreted cautiously. Discussion: Moderate-intensity aerobic exercise in early subacute stroke rehabilitation was not associated with sustained serum brain-derived neurotrophic factor increases compared with relaxation therapy. These findings argue against a robust long-term peripheral neurotrophin response, while not excluding acute, higher-intensity, or subgroup-specific effects.
Summary
Keywords
aerobic exercise, BDNF, neuroplasticity, stroke recovery, subacute stroke
Received
02 June 2026
Accepted
11 August 2026
Copyright
© 2026 Rackoll, Doppelbauer, Neumann and Nave. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Torsten Rackoll
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