Proteoglycan degradation and functional recovery after peripheral nerve injury

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Because damaged axons in peripheral nerves regenerate better than those in the central nervous system, it is assumed that nerve regeneration after peripheral nerve injuries is excellent. However, only a small fraction of adult patients with peripheral nerve injuries will regain full function. The reason most often given for this poor functional recovery is that damaged axons do not regenerate sufficiently to restore function. Using a novel technology, the early regeneration of axons in cut peripheral nerves can be enhanced significantly by the application, at the time of surgical repair, of a mixture of bacterial enzymes which degrade growth inhibitory proteoglycans in the environment of the regenerating axons. Whether this enhancement of early axon regeneration will translate to an enhancement of muscle reinnervation and functional recovery is not known. The goal of this R21 application is to begin to evaluate functional recovery after peripheral nerve injury using this new technology. The time course and extent of restitution of motor and sensory reinnervation of muscles and the recovery of normal muscle activity and ankle joint movements will be studied in rats after transection and surgical repair of the sciatic nerve. To evaluate the timing and extent of reinnervation of muscles, direct muscle and H-reflex activity will be recorded using chronically implanted EMG wire electrodes in response to electrical stimulation of the cut and surgically repaired nerve above the lesion site. To evaluate the return of muscle function, EMG activity will be recorded from the soleus and medial gastrocnemius muscles and ankle joint kinematics will be monitored during walking on a treadmill on level ground and both up and down grades. In rats treated with a mixture of chondroitinase ABC, heparinase I, and heparinase III, these functional outcome measures will be compared to those obtained from a group of animals whose nerves have been cut and repaired but who received no other treatments. The poor recovery following peripheral nerve injuries remains an important clinical problem and may have the added untoward effect of discouraging treatment seeking by affected patients. This proposal seeks to evaluate a technology for medical treatment of peripheral nerve injuries which, if successful, could have an important impact on a relatively large group of under-treated patients.