Dynamics of Circulating Brain-Derived Neurotrophic Factor and Selenoprotein P in Subacute Stroke Patients Undergoing High-Intensity Interval Training-Based Neurorehabilitation: A Pilot Observational Study

Background/Objectives: Brain-derived neurotrophic factor (BDNF) and antioxidant networks mediated by Selenoprotein P (SEPP1) are core drivers of structural neuroplasticity and blood–brain barrier integrity, yet their co-regulatory behavior during subacute stroke neurorehabilitation remains poorly understood. This pilot study quantified concurrent changes in serum BDNF and SEPP1 during rehabilitation. Methods: Sixteen subacute post-stroke patients with mild stroke severity were assigned to an intensive multi-modal neurorehabilitation protocol incorporating high-intensity interval training (Treated, n = 7) or standard care (Control, n = 9); the biomarker sampling window averaged 73.4 days. Fasting venous blood was collected at baseline and post-intervention and analyzed by ELISA. Results: BDNF changes (ΔBDNF) differed significantly between arms (U = 57.0, p = 0.0081): the Treated cohort showed a uniform decrease (mean Δ: −0.240 ± 0.103 ng/mL), while Controls showed stabilization or a slight increase (mean Δ: +0.118 ± 0.339 ng/mL). ΔBDNF and ΔSEPP1 were significantly, positively correlated across the cohort (ρ = 0.596, p = 0.015). Conclusions: The BDNF decline in the Treated group is consistent with the “central sink” hypothesis, but may more plausibly reflect stress/cortisol-mediated suppression induced by the high training intensity, contrasting with increases typically reported after moderate-intensity subacute-phase exercise. The collinear coupling with SEPP1 suggests a link between neurotrophic synthesis and antioxidant buffering during post-stroke tissue remodeling, though this correlational finding does not by itself establish a single, coordinated mechanism.