The phosphatidylinositol-3 kinase/Akt pathway mediates VEGF's neuroprotective activity and induces blood brain barrier permeability after focal cerebral ischaemia

Aims: Based on its trophic influence on neurons and vascular cells, vascular endothelial growth factor (VEGF) is a promising candidate for stroke treatment. VEGF's survival-promoting effects are purchased at the expense of an increased blood brain barrier permeability, which potentially compromises tissue survival. The mechanisms via which VEGF protects the brain against ischemia remained unknown. Methods and results: We examined signaling pathways underlying VEGF's neuroprotective activity in our transgenic mouse line that expresses human VEGF165 under a neuron-specific enolase (NSE) promoter. We show that VEGF…