OBJECTIVE: To provide a novel overview of the literature and to summarise the evidence for the effects of aerobic exercise (AE) on serum biomarkers neuroplasticity and brain repair in stroke survivors. DATA SOURCE: We conducted a systematic review and searched Medline, Embase and Cochrane CENTRAL using terms related to AE, neuroplasticity, brain repair, and stroke. STUDY SELECTION: Titles, abstracts, and selected full texts were screened by two independent reviewers against the following inclusion criteria: studies including adult stroke survivors, completing an AE intervention working within the AE capacity, with at least one blood biomarker outcome of interest measured. DATA EXTRACTION: Two independent reviewers extracted data and assessed risk of bias using Risk of Bias In Non-randomised Studies of Interventions (ROBINS-I) and Cochrane's Risk of Bias 2 (RoB2) tools. DATA SYNTHESIS: Nine studies (n = 215 participants) were included, reporting on the following outcomes: brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), cortisol, interleukin-6 (IL-6) and myeloperoxidase (MPO). A single bout of high-intensity interval training significantly increased BDNF, IGF-1 and VEGF levels, and a 40 to 45-minute, 24-session, continuous eight-week AE training program significantly increased BDNF levels. No significant difference in response to any other AE intervention was found in other serum biomarkers. CONCLUSION: AE can significantly increase BDNF, IGF-1 and VEGF across different AE protocols in stroke survivors. However, more research is needed to determine the optimal exercise intensity and modalities, specifically in acute and subacute stroke survivors, and how this may relate to functional outcomes.

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