Chondroitinase ABC reduces time to muscle reinnervation and improves functional recovery after sciatic nerve transection in rats.

Application of chondroitinase ABC (ChABC) to injured peripheral nerves improves axon regeneration, but it is not known whether functional recovery is also improved. Recordings of EMG activity [soleus (Sol) M response and H reflexes] evoked by nerve stimulation and of Sol and tibialis anterior (TA) EMG activity and hindlimb and foot kinematics during slope walking were made to determine whether ChABC treatment of the sciatic nerve at the time of transection improves functional recovery. Recovery of evoked EMG responses began as multiple small responses with a wide range of latencies that eventually coalesced into one or two more distinctive and consistent responses (the putative M response and the putative H reflex) in both groups. Both the initial evoked responses and the time course of their maturation returned sooner in the ChABC group than in the untreated (UT) group. The reinnervated Sol and TA were coactivated during treadmill locomotion during downslope, level, and upslope walking throughout the study period in both UT and ChABC-treated rats. By 10 wk after nerve transection and repair, locomotor activity in Sol, but not TA, had returned to its pretransection pattern. There was an increased reliance on central control of Sol activation across slopes for both groups as interpreted from elevated prestance Sol EMG activity that was no longer modulated with slope. Limb length and orientation during locomotion were similar to those observed prior to nerve injury during upslope walking only in the ChABC-treated rats. Thus treatment of cut nerves with ChABC leads to improvements in functional recovery.

Effect of axon misdirection on recovery of electromyographic activity and kinematics after peripheral nerve injury.

In this study, patterns of activity in the soleus (Sol) and tibialis anterior (TA) muscles and hindlimb kinematics were evaluated during slope walking in rats after transection and surgical repair either of the entire sciatic nerve (Sci group) or of its two branches separately, the tibial and common fibular nerves (T/CF group). With the latter method, axons from the tibial and common fibular nerves could not reinnervate targets of the other nerve branch after injury, reducing the opportunity for misdirection. Activity in the TA shifted from the swing phase in intact rats to nearly the entire step cycle in both injured groups. Since these changes occur without misdirection of regenerating axons, they are interpreted as centrally generated. Sol activity was changed from reciprocal to that of TA in intact rats to coactivate with TA, but only in the Sci group rats. In the T/CF group rats, Sol activity was not altered from that observed in intact rats. Despite effects of injury that limited foot movements, hindlimb kinematics were conserved during downslope walking in both injury groups and during level walking in the T/CF group. During level walking in the Sci group and during upslope walking in both groups of injured rats, the ability to compensate for the effects of the nerve injury was less effective and resulted in longer limb lengths held at more acute angles throughout the step cycle. Changes in limb movements occur irrespective of axon misdirection and reflect compensatory changes in the outputs of the neural circuits that drive locomotion.

Effect of slope and sciatic nerve injury on ankle muscle recruitment and hindlimb kinematics during walking in the rat.

Slope-related differences in hindlimb movements and activation of the soleus and tibialis anterior muscles were studied during treadmill locomotion in intact rats and in rats 4 and 10 weeks following transection and surgical repair of the sciatic nerve. In intact rats, the tibialis anterior and soleus muscles were activated reciprocally at all slopes, and the overall intensity of activity in tibialis anterior and the mid-step activity in soleus increased with increasing slope. Based on the results of principal components analysis, the pattern of activation of soleus, but not of tibialis anterior, changed significantly with slope. Slope-related differences in hindlimb kinematics were found in intact rats, and these correlated well with the demands of walking up or down slopes. Following recovery from sciatic nerve injury, the soleus and tibialis anterior were co-activated throughout much of the step cycle and there was no difference in intensity or pattern of activation with slope for either muscle. Unlike intact rats, these animals walked with their feet flat on the treadmill belt through most of the stance phase. Even so, during downslope walking limb length and limb orientation throughout the step cycle were not significantly changed from values found in intact rats. This conservation of hindlimb kinematics was not observed during level or upslope walking. These findings are interpreted as evidence that the recovering animals adopt a novel locomotor strategy that involves stiffening of the ankle joint by antagonist co-activation and compensation at more proximal joints. Their movements are most suitable to the requirements of downslope walking but the recovering rats lack the ability to adapt to the demands of level or upslope walking.