{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:03:03Z","timestamp":1789448583879,"version":"build-2803163510"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010571","name":"Bundesministerium f\u00fcr Bildung, Wissenschaft, Forschung und Technologie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010571","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Stroke"],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The early phase after stroke is considered a period of heightened neuroplasticity and may be responsive to rehabilitation interventions targeting biological recovery. Brain-derived 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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 4 weeks of moderate-intensity treadmill-based aerobic training or relaxation therapy. Serum brain-derived neurotrophic factor was assessed from baseline to 6 months post-stroke. Models were adjusted for baseline brain-derived neurotrophic factor, age, sex, stroke severity, platelet count, depressive symptoms, smoking status, and study center.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 200 randomized participants, serum brain-derived neurotrophic factor increased modestly from baseline to 3 months and remained stable thereafter. No relevant between-group difference was observed at 6 months after aerobic training compared with relaxation therapy (training: 24.6 ng\/mL; 95% CI, 20.2\u201329.0 vs. relaxation: 24.3 ng\/mL; 95% CI, 19.8\u201328.8; adjusted\n                      <jats:italic>p<\/jats:italic>\n                      = 0.74). Findings were consistent in complete-case and change-score 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:ext-link>clinicaltrials.gov\/study\/NCT01953549<\/jats:ext-link>\n                      ], identifier [NCT01953549].\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fstro.2026.1897859","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:27:27Z","timestamp":1789446447000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum BDNF in subacute stroke: effects of a four-week aerobic exercise intervention in the PHYS-STROKE trial"],"prefix":"10.3389","volume":"5","author":[{"given":"Torsten","family":"Rackoll","sequence":"first","affiliation":[{"name":"Department for Neurology with Experimental Neurology, Charit\u00e9\u2014University Medical Center Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt\u2013Universit\u00e4t zu Berlin","place":["Berlin, Germany"]},{"name":"QUEST Center for Responsible Research, Berlin Institute of Health at Charit\u00e9\u2014University Medical Center Berlin","place":["Berlin, Germany"]},{"name":"German Center for Cardiovascular Disease (DZHK), Partner Site Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Doppelbauer","sequence":"additional","affiliation":[{"name":"Department for Gynecology with Breast Center, Charit\u00e9\u2014University Medical Center Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt\u2013Universit\u00e4t zu Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department for Neurology with Experimental Neurology, Charit\u00e9\u2014University Medical Center Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt\u2013Universit\u00e4t zu Berlin","place":["Berlin, Germany"]},{"name":"Institute of Biometry and Clinical Epidemiology, Charit\u00e9\u2014University Medical Center Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Heinrich","family":"Nave","sequence":"additional","affiliation":[{"name":"Department for Neurology with Experimental Neurology, Charit\u00e9\u2014University Medical Center Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt\u2013Universit\u00e4t zu Berlin","place":["Berlin, Germany"]},{"name":"German Center for Cardiovascular Disease (DZHK), Partner Site Berlin","place":["Berlin, Germany"]},{"name":"Center for Stroke Research Berlin, Charit\u00e9\u2014University Medical Center Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt\u2013Universit\u00e4t zu Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"637","DOI":"10.3389\/fneur.2018.00637","article-title":"Post-stroke BDNF concentration changes following physical exercise: a systematic review","volume":"9","author":"Alcantara","year":"2018","journal-title":"Front. 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