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Local substitution of GDF-15 improves axonal and sensory recovery after peripheral nerve injury

Abstract

The growth/differentiation factor-15, GDF-15, has been found to be secreted by Schwann cells in the lesioned peripheral nervous system. To investigate whether GDF-15 plays a role in peripheral nerve regeneration, we substituted exogenous GDF-15 into 10-mm sciatic nerve gaps in adult rats and compared functional and morphological regeneration to a vehicle control group. Over a period of 11 weeks, multiple functional assessments, including evaluation of pinch reflexes, the Static Sciatic Index and of electrophysiological parameters, were performed. Regenerated nerves were then morphometrically analyzed for the number and quality of regenerated myelinated axons. Substitution of GDF-15 significantly accelerated sensory recovery while the effects on motor recovery were less strong. Although the number of regenerated myelinated axons was significantly reduced after GDF-15 treatment, the regenerated axons displayed advanced maturation corroborating the results of the functional assessments. Our results suggest that GDF-15 is involved in the complex orchestration of peripheral nerve regeneration after lesion.

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Acknowledgments

This work was financially supported by the International Foundation Neurobionic (grant to K.H.T.). For excellent technical assistance, we thank Silke Fischer, Natascha Heidrich, Jennifer Metzen and Silvana Taubeler-Gerling.

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Conflicts of interest are disclosed for all authors of this work.

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Correspondence to Kirsten Haastert-Talini.

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Mensching, L., Börger, AK., Wang, X. et al. Local substitution of GDF-15 improves axonal and sensory recovery after peripheral nerve injury. Cell Tissue Res 350, 225–238 (2012). https://doi.org/10.1007/s00441-012-1493-6

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Keywords

  • GDF-15
  • Peripheral nerve regeneration
  • Functional recovery
  • Nerve morphometry
  • Epineurial pouch technique