possibility of direct neuroprotective VEGF actions in ischemic tissue in the interval preceding angiogenesis may help prolong cell survival until angiogenesis can occur.

VEGF neuroprotection is exerted mainly by the activation of the VEGFR-2. Additional evidence for direct neuronal protection by VEGF is that VEGF inhibits the death of cultured hippocampal neurons from glutamate and N-methyl-d-aspartate toxicity and that deletion of the hypoxia-response element from the VEGF promoter causes motor neuron degeneration in mice.

Because neuroprotective effects of other growth factors are associated with improved outcome from stroke, this could be true for VEGF as well. Finally, VEGF has been implicated as a factor that

promotes neurogenesis in the adult brain. One possibility is that this occurs through the establishment of a vascular niche that favors the proliferation and differentiation of neuronal precursors, perhaps by the release of BDNF from endothelial cells. Alternatively, VEGF may exercise a direct mitogenic effect on neuronal precursors.

Thus, VEGF expression in the ischemic brain could contribute to ischemia-induced neurogenesis and modify outcome in that way as well.

Intravitreal VEGF inhibition therapy and neuroretina toxicity

The neuroprotective function of VEGF-A in the retina has not been characterized despite the fact