gms | German Medical Science

Objective: Treatment of peripheral nerve injury today includes pain relief medication and often surgery. Up to now, no pharmacological treatment is available to actually promote axonal outgrowth and nerve regeneration. Although several rodent studies are dealing with the identification of molecular mechanisms possible to promote regeneration, little is known about the reaction in human nerves. In this study we use an ex vivo model to investigate processes induced in human nerves upon injury and compare them to murine nerves. Thereby we intend to evaluate mice as model organisms for peripheral nerve injury.

Methods: For our study, we use human sural nerves, which are surgically removed in order to be used as autografts. Since in those kind of surgeries parts of the nerve are often not needed and therefore discarded, we could use those part for our experiments. Nerves of up to 25 patients aged between 20 and 75 years were analysed and compared to sural nerves of mice in terms of gene expression and morphological changes upon injury. The time point of surgical removal (humans) or dissection (mice) was defined as zero time point and used as control uninjured nerve. Parts of the available nerve of each patient were incubated for up to 48 hours and analysed at different time points.

Results: We confirmed that human and murine nerves in the used ex vivo injury system undergo the expected degeneration process. Axons begin to degenerate rapidly upon injury and Schwann cells change their morphology losing their contacts to the axons. Gene expression analysis revealed an injury induced differential gene expression profile in Schwann cells of both organisms. Although the reaction of human Schwann cells was detectable, murine Schwann cells seem to react quicker/stronger to the stimulus of injury. We identified different metabolic changes in murine Schwann cells, which show an adaption of those cells to the altered needs in an injured nerve. This adaption was strongly limited in human nerves. This could in part explain the enhanced regenerative capacity in murine compared to human nerves.

Conclusion: Rodent models of peripheral nerve injury are suitable for the investigation of some processes, which are comparable in human and mice. In addition, identified differences between mice and humans can be used to develop novel therapeutic approaches in order to promote axon growth and nerve regeneration in human patients.