Multisystem neuroprosthetic training improves bladder function after severe spinal cord injury.

UNLABELLED: Severe spinal cord injury leads to neurogenic bladder dysfunction. We recently developed a multisystem neuroprosthetic training program that promotes plastic changes capable of restoring refined locomotion in rats with severe spinal cord injury. We investigated whether multisystem neuroprosthetic training would influence the development of posttraumatic bladder dysfunction. MATERIALS AND METHODS: Eight and 4 adult rats were randomly assigned to a spinal cord injury and an intact control group, respectively. Spinal cord injury consisted of 2 opposite lateral hemisections (T7 and T11), thus, interrupting all direct supraspinal input. After spinal cord injury 4 rats were subjected to a multisystem neuroprosthetic training program and 4 were not trained. At 8 weeks we performed urodynamics and evaluated kidney function using creatinine and cystatin C. Bladder investigation included morphological, histological and immunohistochemical evaluations. RESULTS: Bladder capacity increased threefold in trained and sevenfold in nontrained rats compared to intact rats. During filling we found a mean ± SEM of 2.7 ± 1.1 vs 12.6 ± 5.2 nonvoiding contractions in trained vs nontrained rats. Bladder morphology was similar in trained and intact rats. Nontrained rats showed detrusor hypertrophy, characterized by increased detrusor thickness and a decreased connective tissue-to-smooth muscle ratio. As labeled with protein gene product 9.5, general nerve density was significantly increased in trained and significantly decreased in nontrained rats. The relative proportion of neurofilament 200 positive afferent nerves was significantly lower in trained than in intact and nontrained rats. Neuropeptide Y positive fibers showed significantly lower density in nontrained rats. CONCLUSIONS: Multisystem neuroprosthetic training effectively counteracts the formation of neurogenic bladder dysfunction after severe spinal cord injury and might contribute to preserving bladder function and preventing long-term complications in patients with severe spinal cord injury.

Multi-system neurorehabilitative strategies to restore motor functions following severe spinal cord injury.

Severe spinal cord injury (SCI) permanently abolishes motor functions caudal to the lesion. However, the neuronal machinery sufficient to produce standing and stepping is located below most SCI, and can be reactivated with training. Therefore, why do rats and humans fail to regain significant levels of motor control after a severe SCI? In this review, we argue that the lack of sustainable excitability in locomotor circuitries after SCI prevents the emergence of functional motor states during training, thus limiting the occurrence of activity-dependent plasticity in paralyzed subjects. In turn, we show that spinal rats trained with combinations of epidural electrical stimulation and monoamine agonists, which promote locomotor permissive states during rehabilitation, can regain coordinated stepping with full weight bearing capacities in the total absence of supraspinal influences. This impressive recovery of function relies on the ability of spinal circuitries to utilize multisensory information as a source of control and learning after the loss of brain input. We finally discuss the implication of these findings for the design of multi-system neurorehabilitative interventions capable of restoring some degree of function in humans with severe SCI.

Restoring voluntary control of locomotion after paralyzing spinal cord injury.

Half of human spinal cord injuries lead to chronic paralysis. Here, we introduce an electrochemical neuroprosthesis and a robotic postural interface designed to encourage supraspinally mediated movements in rats with paralyzing lesions. Despite the interruption of direct supraspinal pathways, the cortex regained the capacity to transform contextual information into task-specific commands to execute refined locomotion. This recovery relied on the extensive remodeling of cortical projections, including the formation of brainstem and intraspinal relays that restored qualitative control over electrochemically enabled lumbosacral circuitries. Automated treadmill-restricted training, which did not engage cortical neurons, failed to promote translesional plasticity and recovery. By encouraging active participation under functional states, our training paradigm triggered a cortex-dependent recovery that may improve function after similar injuries in humans.