Exercise is known to aid functional recovery following
ischemia, though the mechanisms responsible for the beneficial effects of exercise on recovery from
ischemic stroke are not fully understood.
Basic fibroblast growth factor (bFGF) contributes to angiogenesis and promotes neurologic functional recovery after
stroke. The present study aimed to investigate the possible mechanisms whereby treadmill exercise ameliorated impaired angiogenesis and neurogenesis following
transient cerebral ischemia in
middle cerebral artery occlusion (MCAO) rats. Treadmill exercise was started 2days after
ischemia-reperfusion in MCAO rats and continued until 7 or 28days after MCAO, after which the animals were sacrificed. Changes in neurological deficit,
infarction volume, neuronal morphology, expression levels of bFGF,
caveolin-1, and
vascular endothelial growth factor (
VEGF), and angiogenesis and neurogenesis in the ischemic penumbra were examined by reverse transcription-polymerase chain reaction, western blots, and/or double immunofluorescence. The results suggested that treadmill exercise promoted the expression of bFGF, improved neurological recovery, and reduced
infarct volume compared with non-exercised rats, and also enhanced the expression of
caveolin-1,
VEGF,
VEGF receptor 2(FIK-1)/CD34, and
Brdu/
nestin staining.
Small interfering RNA targeting bFGF blocked the protective effects of bFGF. In addition, 4weeks of post-
stroke recovery still ameliorated
ischemia-induced damage without bFGF
shRNA. These findings suggest a novel mechanism underlying the beneficial effects of bFGF following
stroke, and indicate that treadmill exercise may aid
stroke recovery by regulating the
caveolin-1/
VEGF pathway in the ischemic zone.