Vascular endothelial growth factor promotes functional recovery after focal cerebral ischemia: role of extracellular matrix and guidance molecules in enhancing axonal plasticity
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor, which also has neuroprotective activity. In view of these dual actions on vessels and neurons, we were interested whether VEGF promotes long distance axonal plasticity in the ischemic brain. Herein we show that VEGF promotes neurological stroke recovery when delivered in a delayed way starting 3 days after middle cerebral artery occlusion. Using anterograde tract tracing experiments that we combined with histochemical and molecular biological studies we demonstrate that although VEGF promoted angiogenesis predominantly in the ischemic hemisphere, where neuroprotection was noticed, pronounced axonal sprouting was induced by VEGF in the contralesional, but not the ipsilesional corticobulbar system. Corticobulbar plasticity was accompanied by the transient downregulation of the axonal growth inhibitors NG2 proteoglycan and brevican and the guidance molecules ephrin B1/2 in the contralesional hemisphere. The regulation of matrix proteinases, growth inhibitors and guidance molecules offers insights how brain plasticity is controlled in the ischemic brain.
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