Ciliary neurotrophic factor promotes motor reinnervation of the musculocutaneous nerve in an experimental model of end-to-side neurorrhaphy

Abstract

BackgroundIt 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.ResultsVehiculum 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.ConclusionThe 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.

End-to-side neurorrhaphy in brachial plexus reconstruction

“…In experimental models, there were no signs of denervation of the donor nerve after creation of a perineurial window. 2,6,8 Similarly, none of the patients in the present study had any sensory or motor loss in the innervation zone of the donor nerve. This is in contrast to fascicular transfer, which uses a fascicle of the ulnar or median nerve for neurotization of the musculocutaneous nerve.…”

“…Without the contribution of the injured axons, the outcome of ESTN would be very poor since only about 1.4% of motor neurons with intact axons can send out collateral branches. 6 Several experimental studies have suggested that sensory reinnervation is superior to motor reinnervation after ETSN. The explanation for better sensory reinnervation after ETSN may lie in the higher total number of sensory fibers than number of motor fibers contributing to the reinnervation.…”

“…1,2,8,11 In addition, only a limited number of motor neurons have the capacity to send out collateral sprouts from intact axons. 6 Few clinical studies dealing with ETSN are available, and those that are represent mainly either case reports or reports involving only a few patients. 16,17,21 In brachial plexus surgery, the ETSN technique can only be performed in patients with an upper brachial plexus palsy.…”

End-to-side versus end-to-end neurorrhaphy at the peroneal nerve in rats

“…This fact allows new treatment possibilities to several different nerve injurie [12][13][14][15][16] . The axonal lateral sprouting occurs after the absortion of the three-conjuntival layers: epineurium, perineurium and endoneurium 17 .…”

Experimental research on end-to-side anastomosis of peripheral nerves and effect of FK506 on end-to-side anastomosis

“…As a method for neural restoration, the end-to-side anastomosis of peripheral nerves repairs nerves through lateral branch sprouting with the normal nerve as a donor without infl uencing the functions of the donor nerve. In recent years, extensive and in-depth researches have been conducted worldwide and some clinical applications have been performed (3). The dominating muscles lose innervation, atrophy, degenerate and fi brillate after peripheral nerves are injured.…”