Femke Mathot

Chapter 1 16 cells start secreting trophic factors as a response to the injury. 13, 28, 29 A so called growth cone is formed at the proximal nerve stump. 30, 31 Angiogenic trophic factors (like VEGF-a) stimulate angiogenesis, which provides the needed oxygen and nutrients to align the proliferating Schwann cells in ‘Bands of Büngner’. 32, 33 These bands guide regenerating axons, enhanced by neurotrophic factors (like NGF, BDNF, GDNF) that are produced by Schwann cells and neurons, in the right direction. 34 Extracellular matrix components are rebuild as a result of the expression and secretion of extracellular matrix proteins by Schwann cells. 28 Eventually, remyelination and reinnervation occurs and the phenotype of Schwann cells is reversed back to a myelinating phenotype. 35 This process is illustrated in figure 2 . Presence of angiogenic trophic factors, neurotrophic factors and extracellular matrix proteins at the regenerating nerve stump facilitates axon regeneration and should therefore be considered as target to improve outcomes of nerve injuries. Figure 2. The process of Wallerian degeneration and nerve regeneration. After nerve injury, activated macrophages phagocytose the axonal and myelin debris. Activated Schwann cells, macrophages and neurons secrete trophic factors that initiate the formation of Bands of Bügner, resulting in axon regeneration. Absence of those essential factors can lead to poor nerve regeneration, scar tissue formation and end organ degeneration. (Used with permission of Mayo Foundation for Medical Education and Research, all rights reserved.)