Increased serum brain-derived neurotrophic factor with high-intensity interval training in stroke patients: A randomized controlled trial

Background: Physiological adaptations of stroke patients after high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) remain unclear. Objective: This study determined the HIIT and MICT effects on aerobic capacity, cerebral oxygenation, peak cardiac output (CO), and serum brain-derived neurotrophic factor (BDNF) in stroke patients. Methods: We included 23 stroke patients with age about 55 years and stroke duration > 24 months; participants completed 36 sessions of exercise training for 30 min; 13 were randomly assigned to perform MICT at 60% of peak oxygen consumption (VO_2peak) and 10 to perform HIIT at alternating 80% (3 min) and 40% (3 min) VO_2peak. Before and after interventions, we evaluated VO_2peak, peak CO, arteriovenous oxygen difference (AV O_2diff), bilateral frontal cortex oxygenation (relative changes of oxyhemoglobin Δ[O₂Hb], deoxyhemoglobin Δ[HHb], and total hemoglobin Δ[THb] levels), serum brain-derived neurotrophic factor (BDNF) level, and fluorescent cell staining for neuron morphology and percentage of cell-bearing neurites (% neurites). Results: HIIT induced significant increases in VO_2peak (P = 0.008), CO (P = 0.038), Δ[HHb] (P = 0.046), Δ[THb] (P = 0.046), and serum BDNF level (P = 0.012). The improvement in VO_2peak was significantly greater with HIIT than MICT (20.7% vs. 9.8%, P = 0.031), as was AV O_2diff (P = 0.041), Δ[HHb] (P = 0.027), and serum BDNF level (P < 0.001). HIIT facilitated neuron dendritic protrusions (greater % neurites, P = 0.012) with prominent redistribution of mitochondria. Conclusion: As compared with MICT, HIIT-improved aerobic capacity by increasing systemic tissue O₂ extraction in stroke patients. Increased cerebral O₂ utilization in the involved hemisphere was also identified after HIIT. These physiological adaptations may be associated with increased serum BDNF level. In vitro dendritic growth in neurons treated with serum from HIIT participants may imply significant effects on neuron activities as compared with MICT. ClinicalTrials.gov identifier: NCT04135391.