title: Vav deficiency impedes peripheral nerve regeneration in mice.
abstract: OBJECTIVE
  The regeneration of adult peripheral nerves is a complex, multi-step process that is often incomplete, resulting in pain and/or loss of muscle innervation. Success is based on a fine-tuned interplay of neurons, Schwann cells, fibrocytes and macrophages realizing Wallerian degeneration, fiber regrowth and revascularization. Following trauma, the nerves distal to the injury site undergo Wallerian degeneration, an event that includes the phagocytosis of debris and the formation of Schwann cell scaffolds that guide the sprouting nerve fibers. The actin cytoskeleton is critical to all of these processes; therefore, activators of the cytoskeleton such as Rho GTPases and RhoGEFS such as Vav2 and Vav3 represent attractive targets for therapeutic intervention.
  
  
  METHODS
  Sciatic nerve segments were surgically resected and reconstructed, and the degenerative/regenerative outcomes were compared in wild-type and Vav2/3 double knockout mice.
  
  
  RESULTS
  Vav2/3 knockout nerves showed delayed Wallerian degeneration and revascularization, a broadly control-like morphometry of the regenerated nerves including remyelination, and contradictory motor function recovery, whereby impaired toe spreading was accompanied by enhanced muscle weight recreation.
  
  
  CONCLUSIONS
  The data suggest that Vav2 and Vav3 are required for normal peripheral nerve degeneration/regeneration, revascularization and functional recovery. Functional redundancy, compensatory mechanisms, and muscle (pseudo)hypertrophy, however, impede the understanding of and intervention in Vav-mediated processes.
authors.affiliation: Institute of Biochemistry and Cell Biology, University of Magdeburg, Magdeburg, Germany. gerburg.keilhoff@med.ovgu.de
authors.forename: Gerburg
authors.initials: G
authors.lastname: Keilhoff
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiegand
authors.forename: Hisham
authors.initials: H
authors.lastname: Fansa
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009045:Motor Endplate / Q000502:physiology; D009048:Motor Skills / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000294:innervation / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D051567:Proto-Oncogene Proteins c-vav / Q000172:deficiency / Q000235:genetics*; D020127:Recovery of Function / Q000502:physiology; D012584:Sciatic Nerve / Q000098:blood supply / Q000503:physiopathology / Q000601:surgery; D020426:Sciatic Neuropathy / Q000235:genetics* / Q000503:physiopathology* / Q000601:surgery; D014855:Wallerian Degeneration / Q000235:genetics / Q000503:physiopathology / Q000601:surgery
chemical_list: D051567:Proto-Oncogene Proteins c-vav; C490565:Vav2 protein, mouse; C496622:Vav3 protein, mouse