Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican Accumulation.

Versican is a chondroitin sulfate proteoglycan (CSPG), which deposits in perineurium as a physical barrier and prevents the growth of axons out of the fascial boundary. Several studies have indicated that the chondroitin sulfate (CS) chains on versican have several possible functions beyond the physical barrier, including the ability to stabilize versican core protein in the extracellular matrix. As chondroitin sulfate synthase 1 (Chsy1) is a crucial enzyme for CS elongation, we hypothesized that in vivo knockdown of Chsy1 at peripheral nerve lesion site may decrease CS and versican accumulation, and result in accelerating neurite regeneration. In the present study, end-to-side neurorrhaphy (ESN) in Wistar rats was used as an in vivo model of peripheral nerve injury to evaluate nerve regeneration after surgical intervention. The distribution and expression of versican and Chsy1 in regenerating axons after ESN was studied using confocal microscopy and western blotting. Chsy1 was silenced at the nerve lesion (surgical) site using in vivo siRNA transfection. The results indicated that Chsy1 was successfully silenced in nerve tissue, and its downregulation was associated with functional recovery of compound muscle action potential. Silencing of Chsy1 also decreased the accumulation of versican core protein, suggesting that transient treating of Chsy1-siRNA may be an alternative and an effective strategy to promote injured peripheral nerve regeneration.

Syndecan-3 contributes to the regulation of the microenvironment at the node of Ranvier following end-to­side neurorrhaphy: sodium image analysis.

Syndecan-3 (SDC3) and Syndecan-4 (SDC4) are distributed throughout the nervous system (NS) and are favourable factors in motor neuron development. They are also essential for regulation of neurite outgrowth in the CNS. However, their roles in the reconstruction of the nodes of Ranvier after peripheral nerve injury (PNI) are still unclear. Present study used an in vivo model of end-to-side neurorrhaphy (ESN) for 1-3 months. The recovery of neuromuscular function was evaluated by grooming test. Expression and co-localization of SDC3, SDC4, and Nav1.6 channel (Nav1.6) at regenerating axons were detected by proximity ligation assay and confocal microscopy after ESN. Time-of-flight secondary ion mass spectrometry was used for imaging ions distribution on tissue. Our data showed that the re-clustering of sodium and Nav1.6 at nodal regions of the regenerating nerve corresponded to the distribution of SDC3 after ESN. Furthermore, the re-establishment of sodium and Nav1.6 correlated with the recovery of muscle power 3 months after ESN. This study suggested syndecans may involve in stabilizing Nav1.6 and further modulate the distribution of sodium at nodal regions after remyelination. The efficiency of sodium re-clustering was improved by the assistance of anionic syndecan, resulting in a better functional repair of PNI.