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Thur, July 21

Speaker: Matthias Ziegler, Ph.D., Post-Doctoral Candidate

Title: Neuronal Reconnectivity After OEG Transplantation in Complete Spinally Transected Rats Combined with Robotic Training

Abstract: Spinal Wistar Hannover rats have been shown to have improved hindlimb function after robotic bipedal step training.  In addition hindlimb improvement in spinal rats has also been shown after injections of olfactory ensheathing glia (OEG).  Given the improved motor performances after each of these two treatments, the effects of the combination of these interventions on hindlimb function were studied. The first focus was determining the importance of variability in robotic training by comparing an assist-as-needed step training paradigm which allows for variability in steps and a fixed trajectory paradigm which allows for minimal variability. The resulting robotic training was then used to determine whether OEG could facilitate functional regeneration of neurons and contribute to the improved hindlimb function or if the improvement could be attributed only to changes within the caudal stump of the spinal cord after a complete, mid-thoracic spinal transection was studied. Changes in hindlimb function were assessed using kinematics during stepping and climbing as well as muscle activity recorded through chronically implanted EMG electrodes in the soleus, an ankle extensor, and the tibialis anterior, an ankle flexor. The ability for OEG to facilitate regeneration was analyzed electrophysiologically by transcranially stimulating the brainstem and recording motor evoked potentials (MEP) recorded from the EMG electrodes with and without intrathecal injections of noradrenergic (NA), serotonergic (5-HT) and glycinergic receptor antagonists.  These studies demonstrated that the variability during assist-as-needed training caused less co-activation of agonist-antagonist muscles and therefore enabled a more normal stepping pattern to be learned. When this training was coupled with OEG injections, we saw an enhanced recovery of motor evoked potentials that could be modulated by the injections of antagonists to serotonergic, noradrenergic and glycinergic receptors.  In addition a re-transection of the spinal cord eliminated the evoked potentials, confirming the signal was mediated via functional neuronal regeneration.

Host: Dr. Jayaraman