Tiam Mana Saffari

122 CHAPTER 6 DISCUSSION In this study, gene expression profiles combined with immunohistochemistry staining against neuronal and angiogenic markers in nerve gaps repaired with autograft, allograft and allograft wrapped around with a SIEF f lap to provide vascularization, were analyzed. These studies were conducted to understand the regulatory mechanisms in the physiological microenvironment generated after nerve transplantation and how vascularization of the nerve bed could alter this healing niche. We examined the expression of the most prominent groups of genes that were predicted to play a role in the effect of vascularization on nerve regeneration and compared their expression in autograft, allograft and SIEF nerve samples, two weeks after nerve reconstruction. After nerve trauma, a series of responses occur that involves Wallerian degeneration 24 . During Wallerian degeneration, the axons and myelin degenerate in the distal stump of the axotomized nerve, leading to phenotypic changes that promote axonal regeneration 1,25 . The molecular changes in the paracrine environment, described as the immediate extracellular environment, and the peripheral environment both contribute to form a favorable environment for axonal outgrowth 26 . Angiogenesis Expression for all assessed angiogenic markers including Cd34, Pecam1/Cd31, Vegfa and Mmp2, was increased in allografts wrapped with the SIEF flap compared to autograft and allograft alone. The increase for these markers in SIEF group was shown to be statistically significant compared to autograft. Previous studies revealed that VEGF expression is significantly upregulated during the early phases after nerve trauma, while a strong downregulation was shown in degenerating nerve, suggesting its possible role during the regenerative process 27 . Our results corroborate these findings and could be explained by the fact that the decellularized nerve allograft is free from vascular cells and undergoes revascularization immediately following nerve reconstruction, whereas this is not necessary in autografts. The process of revascularization is upregulated when providing an adipofascial f lap around the nerve allograft. Immunohistochemical staining against CD34 revealed that long-term vascularity is enhanced at 12 and 16 weeks in allografts wrapped with the SIEF flap.