Tiam Mana Saffari

109 THE LOCAL MICROENVIRONMENT OF NERVE ALLOGRAFTS AFTER ANGIOGENESIS 6 INTRODUCTION Traumatic injury to the peripheral nerve results in Wallerian degeneration at the distal stump 1 , causing discontinuation of the nerve and disturbance of blood supply, consequently preventing nutrition delivery 2 . Regeneration of nerve is achieved in a series of actions mediated by vascular endothelial growth factor (VEGF) and Schwann cell migration as a result of hypoxia during trauma 3 . VEGF, originally known as vascular permeability factor (VPF) is a signaling proteinwith vascular permeability activity that plays a role in regulating new blood vessel formation to provide nutrients to the injury site 4,5 . Vasculature also allows endothelial cells to secrete growth factors that can be beneficial for nerve regeneration by interacting with specific cell membrane surface receptors and stimulating signaling pathways that regulate proliferation, survival, migration and differentiation 6,7 . The importance of growth factors as regulators of post-injury tissue repair is well-established, however, direct delivery has not resulted in improved outcomes as postulated 8-10 . This apparent lack of efficacy at present could be due to the incredible complexity of multiple cellular responses during tissue healing, as well as technical obstacles related to management of the local delivery and pharmacokinetics of growth factors. Recipient gene expression is profoundly altered after nerve transplantation, however, these complex molecular events and cellular responses are neither fully understood nor easy to dissect. The biological functions of genes expressed in a paracrine environment influenced by angiogenic and neurotrophic factors, cytokines controlling immune signal transduction, as well as collagenous and non-collagenous extracellular matrix (ECM) proteins are important parameters that are frequently encountered during acute nerve allograft rejection. Combining gene expression profiles with flow cytometry data of immune cells obtained from blood and long-term immunohistochemical staining may provide mechanistic insights into the cellular effect of vascularization on nerve allografts. The purpose of this study was to evaluate the cellular responses that control the healing environment of processed nerve allografts in a rat sciatic nerve defect model after addition of surgical angiogenesis.