title: Ciliary neurotrophic factor promotes motor reinnervation of the musculocutaneous nerve in an experimental model of end-to-side neurorrhaphy.
abstract: BACKGROUND
  It is difficult to repair nerve if proximal stump is unavailable or autogenous nerve grafts are insufficient for reconstructing extensive nerve damage. Therefore, alternative methods have been developed, including lateral anastomosis based on axons' ability to send out collateral sprouts into denervated nerve. The different capacity of a sensory or motor axon to send a sprout is controversial and may be controlled by cytokines and/or neurotrophic factors like ciliary neurotrophic factor (CNTF). The aim of the present study was to quantitatively assess collateral sprouts sent out by intact motor and sensory axons in the end-to-side neurorrhaphy model following intrathecal administration of CNTF in comparison with phosphate buffered saline (vehiculum) and Cerebrolysin. The distal stump of rat transected musculocutaneous nerve (MCN) was attached in an end-to-side fashion with ulnar nerve. CNTF, Cerebrolysin and vehiculum were administered intrathecally for 2 weeks, and all animals were allowed to survive for 2 months from operation. Numbers of spinal motor and dorsal root ganglia neurons were estimated following their retrograde labeling by Fluoro-Ruby and Fluoro-Emerald applied to ulnar and musculocutaneous nerve, respectively. Reinnervation of biceps brachii muscles was assessed by electromyography, behavioral test, and diameter and myelin sheath thickness of regenerated axons.
  
  
  RESULTS
  Vehiculum or Cerebrolysin administration resulted in significantly higher numbers of myelinated axons regenerated into the MCN stumps compared with CNTF treatment. By contrast, the mean diameter of the myelinated axons and their myelin sheath thickness in the cases of Cerebrolysin- or CNTF-treated animals were larger than were those for rats treated with vehiculum. CNTF treatment significantly increased the percentage of motoneurons contributing to reinnervation of the MCN stumps (to 17.1%) when compared with vehiculum or Cerebrolysin treatments (at 9.9 or 9.6%, respectively). Reduced numbers of myelinated axons and simultaneously increased numbers of motoneurons contributing to reinnervation of the MCN improved functional reinnervation of the biceps brachii muscle after CNTF treatment.
  
  
  CONCLUSIONS
  The present experimental study confirms end-to-side neurorrhaphy as an alternative method for reconstructing severed peripheral nerves. CNTF promotes motor reinnervation of the MCN stump after its end-to-side neurorrhaphy with ulnar nerve and improves functional recovery of the biceps brachii muscle.
authors.affiliation: Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, and Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 3, CZ-625 00 Brno, Czech Republic. pdubovy@med.muni.cz
authors.forename: Petr
authors.initials: P
authors.lastname: Dubový
authors.forename: Otakar
authors.initials: O
authors.lastname: Raška
authors.forename: Ilona
authors.initials: I
authors.lastname: Klusáková
authors.forename: Lubomír
authors.initials: L
authors.lastname: Stejskal
authors.forename: Pavel
authors.initials: P
authors.lastname: Celakovský
authors.forename: Pavel
authors.initials: P
authors.lastname: Haninec
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000008:administration & dosage*; D005260:Female; D009046:Motor Neurons / Q000187:drug effects*; D009138:Musculocutaneous Nerve / Q000187:drug effects / Q000293:injuries* / Q000503:physiopathology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D016067:Nerve Transfer / Q000379:methods*; D059348:Peripheral Nerve Injuries / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020934:Ciliary Neurotrophic Factor