Research has suggested that people who have higher levels of physical activity before a stroke have better outcomes after the stroke has occurred, but scientists have yet to understand the underlying mechanisms.1
Now a study has found that increased physical activity before a stroke may increase levels of vascular endothelial growth factor (VEGF). The study further found that higher levels of physical activity as well as higher levels of VEGF were linked to improved stroke outcomes and smaller infarct size. Results were published online in the Journal of Stroke and Cardiovascular Diseases.2
“In the present study we have observed that a high level of self-reported physical activity prior to stroke was associated with greater VEGF expression in the first days after ischemic stroke. Likewise, this increment in VEGF levels was independently associated with a reduction in final infarct volume and with improvement of functional outcome at 3 months,” wrote first author Elena Lopez-Cancio, MD, PhD, of the Universidad Autónoma Barcelona (UAB) (Barcelona, Spain), and colleagues.
The study was part of the AFRICA (Prestroke Physical Activity and Functional Recovery in patients with Ischemic stroke and Arterial Occlusion) study. Participants were included if they had experienced an acute ischemic event in the anterior large artery, and were admitted to a single tertiary care stroke center in Barcelona, Spain between June 2008 and January 2011.
Using a validated questionnaire, participants self-reported their physical activity in the past week before the stroke. They also provided blood samples for evaluation of circulating VEGF, granulocyte colony-stimulating factor (G-CSF), and brain-derived neurotrophic factor (BDNF). Levels of these angiogenic and neurogenic factors were evaluated upon admission, at 7 days, and three months post-stroke.
The analysis included 83 patients, with a mean age of 69.6 years.
• VEGF increased from baseline to day 7
♦ This increase was significantly higher in those with higher pre-stroke physical activity vs lower activity (mean increase 30.1 pg/mL versus 14.4 pg/mL, P<0.05)
♦ This increase was linked to significantly better NIHSS stroke severity scores at admission (−031, P=0.004) and at day 7 (−.65, P<0.001)
• Higher prestroke physical activity was linked to smaller infarct volume 30 days post-stroke and better functional outcome at 3 months
• Higher serum VEGF at day 7 was independently linked to smaller infarct volume at 30 days, and improved functional outcome at 3 months
• G-CSF and BDNF were not linked to prestroke physical activity or stroke outcomes
The authors provided several explanations for these results. Past studies have suggested that physical activity may increase VEGF expression. In turn, animal studies have suggested that VEGF may play a role in neuroprotection, neurogenesis, nitric oxide-induced angiogenesis and repair of the postischemic brain. Animals studies have also suggested that VEGF expression in parts of the brain increases after an ischemic event, and this increase has been linked to smaller infarct volume.
If VEGF is neuroprotective, administering it after stroke may improve outcomes, they suggested. Unfortunately, studies that have evaluated post-stroke VEGF delivery show positive but also negative effects, including blood-brain barrier leakage and brain edema. The authors propose that physical activity may be a safe way to increase VEGF production, rather than delivering exogenous VEGF.
“Although there are probably more molecular mechanisms by which physical activity exerts its beneficial effects in stroke outcomes, our observation regarding the potential role of VEGF is plausible and in line with previous experimental studies. Further research in this field is needed,” they concluded.
• A study in Spain found that VEGF increases from baseline to day 7 in patients with ischemic stroke.
• Patients with higher levels of pre-stroke physical activity had greater increases in VEGF than those with lower levels of pre-stroke physical activity.
• Higher increases in VEGF and higher levels of pre-stroke activity were linked to improved functional outcomes at three months, and smaller infarct size at 30 days.
• Physical activity may be one way to increase synthesis of VEGF, which may be neuroprotective in stroke.
• Further studies are needed.
This study was partially supported by the Instituto de Salud Carlos III, the Spanish Research Network on Cerebrovascular Diseases, and the European Union program FEDER. Drs. Campos and Sobrino have received research contracts from Miguel Servet Program of Instituto de Salud Carlos III. Dr. López-Cancio has received a research contract from Juan Rodés program of Instituto de Salud Carlos III.
1. Ricciardi AC, et al. Prestroke physical activity is associated with good functional outcome and arterial recanalization after stroke due to a large vessel occlusion. Cerebrovasc Dis. 2014;37:304-311.
2. López-Cancio E, et al. Reported prestroke physical activity is associated with vascular endothelial growth factor expression and good outcomes after stroke. J Stroke Cerebrovasc Dis. 2016 Oct 28.