Dynamics of serum BDNF After Aerobic Exercise in Subacute Stroke Patients: A Sub-Analysis of the randomized controlled Phys-Stroke trial

During the very early phase of stroke recovery, the brain is hypothesized to be in a neuroplastic state that is responsive to external stimuli. Here, brain-derived neurotrophic factor (BDNF) is thought to play an important role. BDNF, a member of the neurotrophin family, is implicated in processes such as synaptogenesis and long-term potentiation. Post-stroke, reduced BDNF levels are observed compared to the healthy population. An intervention that has been shown to elevate BDNF is Aerobic exercise. Yet, the impact of aerobic exercise in stroke patients remains unclear. This sub-analysis of the multicenter, randomized, controlled Physical Fitness Training in Patients with Subacute Stroke trial aimed to investigate serum BDNF dynamics and the effects of a four-week aerobic exercise intervention on long- term BDNF levels. Data from 200 patients, with missing data imputed, revealed a modest increase in serum BDNF levels up to three months post-stroke (22.6 ng/ml, 95% CI 19.2 to 26) which plateaued until six months (24.3 ng/ml, 95% CI 20.6 to 27.9). Despite higher baseline BDNF levels in the exercise group, no treatment effect was observed until six months (training 24.6 ng/ml, 95% CI 20.2 to 29 vs relaxation: 24.3 ng/ml, 95% CI 19.8 to 28.8, p = 0.95). A sex-related interaction was identified in the relaxation group, with female patients exhibiting higher BDNF increases until end of follow up (20.9 ng/ml, 95% CI 15.7 to 26.2 (males) vs 31.0 ng/ml, 95% CI 22.9 to 39.0 (females), p = 0.039). Dose-response analyses and associations with recurrent events yielded no substantial differences. While serum BDNF levels increased early after stroke in the first three months, aerobic exercise did not demonstrate a significant impact on BDNF levels within this dataset. Further investigations with more measurements during the early subacute phase are warranted to elucidate the interplay between exercise, BDNF, and recovery.