Strategies for promoting neural plasticity after experimental spinal cord injury.

摘要

Repetitive movement therapies such as body weight supported treadmill walking combined with functional electrical stimulation are being utilized to promote recovery of sensorimotor function in people with spinal cord injury (SCI). With the long-term objective of understanding mechanisms by which these therapies may harness neural plasticity to accelerate and enhance sensorimotor recovery, three studies were conducted in an SCI rodent model.;The hypothesis that daily treadmill locomotor therapy could enhance recovery of sensorimotor control in rodents with moderate-severe incomplete SCI was tested in the second study. Kinematics indicated that animals receiving therapy did not develop outward hindlimb rotation deficits during overground walking. All animals receiving therapy versus half without therapy, walked consistently with improved footfall coordination and interlimb kinematics on the treadmill at six weeks post injury. However intralimb joint angle kinematics and hindlimb Hoffman reflexes remained impaired. These impairments could be a result of the altered motoneuron morphology that can occur after severe SCI.;Neuromuscular electrical stimulation (NMES) could provide repetitive movement of specific joints. Hence, an adaptive NMES based intermittent stimulation paradigm (aNMES) was implemented in incomplete SCI rats with implanted intramuscular stimulating electrodes. aNMES automatically and reliably produced specified hip movements, accounting for non-linear muscle recruitment, fatigue and cutaneous spinal reflexes during long stimulation sessions. Sessions could be consistently repeated over multiple days.;Together these studies indicate that changes in motoneuronal structural plasticity may account for impaired motor control after SCI. While the deficits could be ameliorated with the clinically prevalent treadmill training therapy, a more targeted approach using aNMES for specific joints may be needed for recovery of finer motor coordination. Future studies could combine these different strategies to promote neural plasticity after spinal cord injury.;Four motoneuron pools were simultaneously retrogradely labeled with AlexaFluor conjugated cholera toxin beta injected into hindlimb flexor and extensor muscles in chronic SCI (transected or incomplete) and uninjured rats. In transected animals, motoneuron soma size decreased in one pool while somas were elongated in the other three. Changes in form could relate to changes in dendritic arbor scale and orientation and together lead to altered motoneuron function after severe SCI.