Enhanced Regeneration And Functional Recovery After Spinal Root Avulsion By Manipulation Of ChABC With The Antagonism Of PTPσ

Brachial plexus root avulsion is a common injury type of brachial plexus lesions in clinic characterized by the interruption of rootlets from cervical cord, which usually leads to persistent or intermittent neuropathic pain, loss of sensory, motor and autonomic function.Brachial plexus avulsion(BPA) is a combined injury involving peripheral nerve system(PNS) and central nerve system(CNS), which is also called “longitudinal spinal cord injury”. The treatments of BPA is intractable, and the effect of therapies now available in clinical, such as nerve transposition and functional reconstruction ect., are not satisfied. Additionally, there are several side effects and severe commemoratives. Nerve root reimplantation is an emerging therapy for BPA recent years, which has been certified to be effective, to some extent, in repairing motor function of limbs and eschewing side effects. But due to a series of pathophysiologic changes of lesions, the therapeutic effect is unsatisfactory. These changes include massive destruction of nervous tissues, formation of glial scar impeding the regeneration and extend of axons, difficult restoration of the duration between peripheral part and central part etc. There are numerous inhibitory factors in traumatic CNS. It found that the glail scar and chondroitin sulfate proteoglycans(CSPGs) act as significant physical and chemical obstacle in the regeneration of nerve fibres, respectively. The glial scar not only exists in CNS, but in peripheral epineurium, which inhibits the regrowth of axons all the way. With regard to these two inhibitory factors, the primary treatments are the digestion of CSPGs by chondroitinase ABC(Ch ABC) and the application of intracellular sigma peptide(ISP), which is able to against the combination of CSPGs and receptor protein tyrosine phosphatase sigma(PTPRs/PTPσ). For different administration method and function mechanism, we expect to compare the promotion of Ch ABC and ISP in axons regeneration after nerve root reimplantation, and to observe the effect of combination treatment.In this study, the model of nerve roots avulsion was made by posterior approach of cervicothoracic vertebra. During operation, the right C5-C7 dorsal roots were cut and corresponding anterior roots were avulsed, then C6 never rootlet was reimplanted to proper position. The groups and treatments are as follows. Control: cover C6 roots with gelatin sponge containing 10 ul 5%DMSO saline during operation, and inject 500 ul 5%DMSO saline subcutaneously everyday postoperation; Ch ABC group: cover C6 roots with gelatin sponge containing 10 ul 2.5U/ml Ch ABC saline during operation, and inject 500 ul 5%DMSO saline subcutaneously everyday postoperation; ISPgroup: cover C6 roots with gelatin sponge containing 10 ul 5%DMSO saline during operation, and inject 500 ul saline containing 5Um ISP subcutaneously everyday postoperation; Ch ABC+ ISP group: cover C6 roots with gelatin sponge containing 10 ul 2.5U/ml Ch ABC saline during operation, and inject 500 ul saline containing 5Um ISP subcutaneously everyday postoperation.2 weeks postoperation, the postoperative functional outcomes of rats were elevated by Trtzis grooming test weekly. Electromyography and fluorescents labeling was performed at 6 weeks after operation, and the spinal cord specimens were extracted to measure survival rate of motor neurons in ipsilateral C6 segment. Labeling distal and proximal part of ipsilateral musculocutaneous nerve with toluidine blue and choline acetyltransferase(Ch AT), respectively, to observe the regeneration of axons and myelin sheath. The number of motor endplate in biceps and the diameter of biceps were measured to elevate muscle restoration. With various detections as above, we make systemic evaluations of treatment effects in different groups and draw some conclusions:1. Nerve root reimplantation is effective in neural functional recovery to certain extent after BPA.2. The effects of Ch ABC are confined by administration methold and action mechanism,leading to unsatisfactory effectiveness in nerve regeneration and function restoration.3. It confirms the exact curative effect of ISP in Nerve root reimplantation after BPA, which promotes neurological function reconstruction significantly.4. The combination of Ch ABC and ISP is more effective in promoting nerve regeneration and function restoration in Nerve root reimplantation after BPA.5. Ch ABC plays an importment role in neuroprotective effect and axons regeneration, which makes it an adjuvant therapy in BPA. The combination of Ch ABC and other beneficial treatments can preferably promote axons regrowth and function recovery.In conclusion,our study proved that Nerve root reimplantation in BPA is beneficial for nervous function restoration to some extent.The promotion of axons regeneration is different in various groups. Though part of detection indexes in Ch ABC group were beter, most of had no statistical significance and it presented no obvious nerve fibres regrowth,compared to the control.ISP is an effective therapy significantly enhancing axons regeneration and promoting function recovery. The combination of Ch ABC and ISP show a better effectiveness on the basic of ISP, so the monotherapy of Ch ABC is not proposed. With different administration and action mechanism, Ch ABC and ISP can be applied together or combine with other treatments to promote axons regeneration, which provides experimental bases for clinical treatment of BPA.