Spinal cord epidural stimulation and climb training enhance axon regeneration in rats transplanted with olfactory ensheathing cells after a complete spinal cord transection

Implantation of olfactory ensheathing cells (OECs) after a spinal cord lesion has been shown to promote axon regeneration across the lesion site and to promote some functional recovery. In addition, a regimen of rehabilitative motor training facilitates the extent of functional recovery. The spinal cords of 20 adult Sprague Dawley rats were completely transected at ~T8 and randomly assigned to 4 groups (n=5/group). The rats received a transplantation of either OECs or skin fibroblasts (FBs) immediately after the spinal cord transection and were either trained to climb a grid or not trained. Two groups (OEC-Trained, and FB-Trained) began training 2 weeks post-injury. The rats were trained to climb up a grid (1-inch spacing) inclined at 60 degrees for 20 min/day, 3 days/week. During training, the rats received sub-threshold epidural stimulation (40 Hz at L2 and S1). Two other groups (OEC-CSA and FBCSA) were immunosuppressed with cyclosporine A (CSA) for the duration of the study but did not receive any training or epidural stimulation. Transcranial electrical stimulation (TES, singular monophasic pulse, 0.2 Hz) was performed in a non-anaesthetized state to electrophysiologically assess connectivity across the lesion site. Two months post-injury, TES elicited more early responses (ERs) and silent period responses (SPRs) in the hindlimb muscles of trained than non-trained rats. The greatest number of ERs was observed in the OEC-Trained group. At 7 months post-injury, TES was performed after the rats were given a dose of strychnine (0.5 mg/kg body weight, i.p.), a glycine receptor antagonist. Under these conditions, the majority of trained rats showed ERs, whereas only one untrained rat had an ER. TES after strychnine administration also elicited spontaneous bursting responses (SBRs) in the majority of untrained rats but in only 1 trained rat. The variety of responses elicited highlights the advantages of performing TES in awake rats and in rats under the influence of strychnine. These methods allow for the detection of changes in a range of networks projecting to specific muscles. These data also suggest that using strychnine can maximize evidence of supraspinal connectivity by exposing networks that would not be observed without systemic disinhibition. Overall, these results suggest that a training regimen involving grid climbing with epidural stimulation can enhance the regenerative effects of OEC transplantation.

Society for Neuroscience Chicago Nanosymposium Advances in SCI Research and Plasticity

Support: NIH Grant R01NS076976
Authors: A. K. YEUNG, G. GARCIA-ALIAS, K. G. GRIFFIS, R. R. KHANKAN, H. ZHONG, *R. R. ROY, P. E. PHELPS, V. EDGERTON; Integrative Biol. and Physiol., UCLA, Los Angeles, CA
Disclosures: A.K. Yeung: None. G. Garcia-Alias: None. K.G. Griffis: None. R.R. Khankan: None. H. Zhong: None. R.R. Roy: None. P.E. Phelps: None. V. Edgerton: None.

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