Background: Constraint-Induced Movement Therapy (CIMT) is one efficient approach
to improve functional recovery after ischemic stroke. The underlying molecular mechanism remains
unclear. In the current study, we investigated the effects of CIMT on angiogenesis and neurogenesis.
To start linking our findings to molecular mediators, we further examined the expression of
Hypoxia-Inducible Factor-1α (HIF-1α), Factor Inhibiting HIF-1 (FIH-1) and Vascular Endothelial
Growth Factor (VEGF).
Methods: Rats were randomly assigned into three groups: a Middle Cerebral Artery Occlusion
group (MCAO), a therapeutic group (CIMT+MCAO), and a sham middle cerebral artery occlusion
group (Sham). Seven days after surgery, a plaster cast was placed around the unimpaired upper limb
of the rats in the CIMT+MCAO group for 14 days. CIMT was performed on a horizontal ladder.
Neurobehavioral consequences were evaluated using the Open-Field Test (OFT) and the Foot-Fault
Test (FFT). The number of new neurons, the length of vessels as well as the expression of HIF-1α,
FIH-1, and VEGF were examined before and after 14 days of CIMT.
Results: The CIMT+MCAO group showed a significant increase in the total length of microvessels
and increased number of Bromodeoxyuridine+ (BrdU+)/NeuN+ double-labeled cells. These changes
were correlated with an increase in HIF-1α and VEGF expressions and a decrease in
FIH-1expression. FFT showed that the CIMT+MCAO group exhibited marked improvement in
neurobehavioral outcome when compared to the MCAO group. Adverse effects on total activities or
anxiety were not observed using open field analysis.
Conclusion: CIMT-induced neuroprotection and functional recovery following cerebral ischemia
were possibly mediated by an increase in endogenous HIF-1α and VEGF expression with subsequent
neurogenesis and angiogenesis.