Tiam Mana Saffari

123 THE LOCAL MICROENVIRONMENT OF NERVE ALLOGRAFTS AFTER ANGIOGENESIS 6 This improved vascularization is predicted to facilitate nerve graft survival and neural tissue regeneration. Neuronal expression Neurotrophic factors play essential roles in axonal guidance, myelination and neuronal survival 28 . In this study, Gdnf and Ngf expression levels were shown to be near to non- detectable. Gdnf was shown to promote survival of neurons by prevention of apoptosis 15,29 and Ngf to promote Schwann cell activity 30-32 . Yet, these genes were only found to be upregulated in sensory nerves and not in motor nerves 17,33,34 , providing a plausible explanation for these findings. Data on neurotrophic factors is limited and would require additional longitudinal studies with multiple time points to draw definitive conclusions regarding their modulation. Studies presented to date have shown that expression of Gdnf and Ngf is highly variable and clearly fluctuates over the course of the first 21 days in vitro 7 . Long-term results in this study, showed no differences in neuronal expression between groups using immunohistochemistry against PGP 9.5 and S100. Neurotrophic factors after nerve repair are highly variable and require additional studies prior to drawing definitive conclusions. Immunology Two classical subpopulations of T cells are involved in rejection of tissue allografts 35 . In our study, the fraction of CD4 positive T cells measured in peripheral blood were significantly increased in allografts wrapped with the SIEF flap at one week postoperatively. No differences between groups were found for CD8 positive T cell when compared to control baseline levels. A previous study has found a peak of cytotoxic CD8 T cells 35 , but this finding did not replicate under our experimental conditions. Processed decellularized nerve grafts, used in this study, are acellular and are not expected to evoke immune rejection to any large extent that it would result in recruitment of CD8 positive cells to the graft site. Immunotrophic genes showed measurable differences in mRNA levels, but these levels were close to background levels thus precluding definitive interpretation. The alloimmune response involves many cytokines influencing the progression of the response leading to either allograft survival or rejection 36 . Based on these findings, it could be concluded that nerve defect