The role of vascular endothelial growth factor in angiogenesis and brain circulation after stroke

The reparative role of angiogenesis in the maintenance of brain circulation after an acute ischemic stroke (AIS) episode is mediated by cellular signaling cascades orchestrated through many molecules including an essential protein regulator of angiogenesis known as vascular endothelial growth factor (VEGF). [11],[12] The phosphorylation of tyrosine residues within VEGF-A activates its receptor tyrosine kinase activity and causes activation of its downstream target proteins in three important signal transduction pathways: (1) the Akt and phosphatidylinositol-3-kinase (PI3K) pathways, (2) the mitogen-activated protein kinase (MAPK) pathway, and (3) matrix metalloproteinases (MMPs). [13],[14],[15],[16] A recent research study in a rodent middle cerebral artery occlusion (MCAO) model of AIS made four key conclusions: (1) the early secretion of VEGF contributes to endothelial leakiness after AIS, (2) the early inhibition of VEGF may reduce neurovascular permeability along with (3) decreasing infarct volume and increasing neurological functioning, and (4) these neuroprotective effects may decrease MMP 2 and 9 levels and simultaneously increase tight junction proteins such as occludin.