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Purpose: Nerve regeneration and functional recovery are often incomplete after peripheral nerve damage. The aim of this study was to determine if chondroitinase ABC injection at the lesion site, 1 hour of electrical stimulation and the combination of these treatments at the time of repair could be effective in promoting muscle reinnervation., Methods: The right sciatic nerve was completely sectioned in 32 female Sprague-Dawley rats. End-to-end microsuture repair was undertaken and fibrin glue was added. Five groups were studied: 1) suture (S) + fibrin glue (F) only; 2) S + F + chondroitinase ABC; 3) S + F + electrical stimulation; 4) S + F + chondroitinase ABC + electrical stimulation; 5) uninjured nerve., Results: Post recovery kinematics showed larger excursion of the hip-ankle-toe angle during walking in groups 2, 3 and 4 than in group 1 (p < 0.05). In vivo electromyographic activity and maximal muscle force were similar between groups 2, 3, 4 and 5, with higher values in all of them compared to group 1 (p < 0.05). Also, the distal stump of the sciatic nerve was excised, and cross-sectioning revealed that the number of axons were similar in all groups., Conclusions: 150 days after nerve transection, recovery was incomplete with S and F only. Chondroitinase ABC injection at the lesion site and/or 1 hour of electrical stimulation of the proximal nerve stump were beneficial in promoting nerve regeneration and functional muscle reinnervation.

After injury to the mammalian central nervous system (CNS), neurons are not able to regenerate their axons and recovery is limited by restricted plasticity. Axon regeneration is inhibited by the presence of the various inhibitory molecules, including chondroitin sulfate proteoglycans (CSPGs) which are upregulated around the injury site. Plasticity after the end of critical periods is restricted by extracellular matrix changes, particularly the formation of CSPG-containing perineuronal nets. Enzymatic removal of chondroitin sulfate (CS) chains with chondroitinase ABC promotes axon regeneration and reactivates plasticity. This review details the structures and properties of the different CSPGs in the normal and damaged CNS, the use of the enzyme chondroitinase ABC to promote neural regeneration and plasticity, and discusses mechanisms of action and possible therapeutic uses of this enzyme.