The neurovascular link has received increasing interest during the last few years. Not only blood vessels and nerves develop and branch in a similar manner, but also they share common mechanisms for cell signaling and pathfinding. First, there are striking similarities between the growth cone of axons and the endothelial tip cell in blood vessels. Both play a similar role in exploring the environment and function to define the direction in which the axon or the new vascular sprout grows. Second, molecules originally though to be primarily regulators of axon guidance, turned out to be critically important for several aspects of cardiovascular development. Conversely, VEGF, once identified as an endothelial specific growth factor, is now well established to exert direct neuroprotective, neurotrophic and neuroproliferative effects in a variety of neural cell types.
From a therapeutic perspective, the discovery of this neuro-vascular link might also pave the way for the development of novel therapeutic strategies. On one side, VEGF has shown promise in several animal studies as a potential future therapy for nerve injury caused by ischemia, diabetes or degenerative disorders. Though the potent effect of VEGF on vascular leakiness is a potential obstacle to harnessing its therapeutic potential for neural diseases, the experience of recent clinical trials for cardiovascular diseases seems to support the safety and feasibility of VEGF therapy [212, 213]. On the other side, the fact that the mechanisms controlling neural and cardiovascular development intermesh to a remarkable degree offers new therapeutic concepts for both inducing and inhibiting angiogenesis. Initial evidence that interfering with Robo, Semaphorin or ephrins signaling inhibits tumor angiogenesis in different animal models provides a first glimpse of this therapeutic potential [91, 214, 215]. It still remains to be determined whether some of these molecules will be useful for stimulating the reperfusion of ischemic tissues in the clinic, an imperative medical need to date.
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