Tiam Mana Saffari

35 THE ROLE OF VASCULARIZATION IN NERVE REGENERATION 2 excluded. Six exceptionally valuable articles published prior to 1985 were included based on snowballing. MECHANISMS OF VASCULARIZATION Formation of a vascular network of peripheral nerves The processes underlying the formation of blood vessels are vasculogenesis and angiogenesis 17 . Vasculogenesis describes the formation of the primitive vasculature in the embryo. After development of this primary vascular system, remodeling of pre- existing vessels into new areas forms mature vasculature as a result of angiogenesis. Central to the control of angiogenesis is VEGF, which is also critical to the maturation and stabilization of vessels in this process 17 . VEGF-induced effects are mediated through receptor tyrosine kinases, predominantly expressed on endothelial cells 18 . A cadaver study identified five different patterns of blood supply to the nerves varying from no dominant arterial pedicle to multiple dominant arterial pedicles forming a continuous artery that accompanies the nerve 19 . While identifying vascular supply to peripheral nerve contributes to our knowledge, this does not clarify the mechanisms of peripheral nerve revascularization. Revascularization of the nerve The vascular tree and the nervous system branching networks are often patterned similarly in peripheral tissues and share several anatomical and functional characteristics 5 . This parallel pattern has raised questions regarding their interactions to explain whether both networks are independent of one another. In the embryonic limb skin, endothelial cells migrate toward and align with peripheral nerves in response to nerve and Schwann cell-derived VEGF-A; this is called angiogenesis 5 . Subsequently, the pattern of axons provides a spatial template for the pattern of arterial vessel branching resulting in congruence of these two networks. Transplanted nerves have no vascular supply and need to undergo revascularization in the recipient bed 20 . Experimental models have investigated the pattern of endoneurial perfusion. These models provided evidence that the primary mechanism of