Treadmill locomotor training and neurotrophic factors: their effect on locomotor recovery and spinal modularity in the chronic spinal cat

Vanessa Susanne Boyce

doi:10.17918/00000489

Globally, spinal cord injury (SCI) affects tens of thousands of people annually, and depending on the severity and location of the trauma, can be debilitating. Therapies for the treatment of SCI use many different approaches to restore function. In this work two established approaches, transplantation and rehabilitation, were combined. We introduced neurotrophic factors into a complete spinal lesion via genetically engineered fibroblasts and provided locomotor training to the spinal cats. The locomotor recovery with each treatment alone and in combination was compared to the recovery in control cats (Op-control) that received unmodified fibroblast graft and no locomotor training. Op-control animals could not locomote. However, plantar weight bearing stepping was restored in cats receiving training only (Trained), neurotrophic factors only (NTF), and cats with the combination treatment (Combination). The latter group of cats was superior in some metrics of gait. Histological examination showed axonal sprouting within the graft for all cats. Thus we demonstrated that (1) both modified and unmodified grafts supported axonal sprouting, (2) grafts secreting neurotrophic factors alone were sufficient to restore locomotor function and (3) the combination therapy of training and neurotrophic factor administration was beneficial in enhancing some aspects of locomotion in the spinal cat. To determine how SCI and/or our interventions influenced motor responsiveness in the spinal cord caudal to the injury, we examined the endpoint force pattern types produced by intraspinal microstimulation of the interneuronal lumbar circuitry. We demonstrated that chronic SCI altered the proportion and distribution of endpoint force pattern types compared to the uninjured cat. The threshold for activation was also lowered. Hindlimb electromyographic activity recorded during intraspinal microstimulation was highly dependent upon hindlimb position. Therefore chronic SCI modified the motor output of the L5-L7 spinal cord. Overall, the modularity in motor output was preserved after injury, although the frequency at which some of the response types were expressed was modified by injury and to a lesser extent by training. The results illuminate the complexity of the locomotor spinal circuitry, and the importance of understanding how injury affects the spinal cord in order to design targeted treatments.

Treadmill locomotor training and neurotrophic factors: their effect on locomotor recovery and spinal modularity in the chronic spinal cat

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Treadmill locomotor training and neurotrophic factors: their effect on locomotor recovery and spinal modularity in the chronic spinal cat

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