Although several studies suggest that an upregulation of VEGF may fulfill a protective and neurotropic function, and that administration of VEGF may improve diabetic neuropathy, other studies show that an increase in circulating VEGF levels is associated with pathological angiogenesis and changes in vascular permeability, thereby contributing to cardiovascular and diabetic complications, ischemia of nerve fibers and hypoxia (Figure 2) (48, 270–274). Here, VEGFA is linked to diabetic neuropathy.