摘要
As most spinal cord injuries （SCIs） are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal motor circuits. Among the pathways, the corticospinal tract （CST） is most associated with skilled voluntary functions in humans and many animals. CST loss, whether at its origin in the motor cortex or in the white matter tracts subcortically and in the spinal cord, leads to movement impairments and paraly- sis. To restore motor function after injury will require repair of the damaged CST. In this review, I discuss how knowledge of activity-dependent development of the CST--which establishes connectional speci- ficity through axon pruning, axon outgrowth, and synaptic competition among CST terminals--informed a novel activity-based therapy for promoting sprouting of spared CST axons after injur in mature animals. This therapy, which comprises motor cortex electrical stimulation with and without concurrent trans-spi- nal direct current stimulation, leads to an increase in the gray matter axon length of spared CST axons in the rat spinal cord and, after a pyramidal tract lesion, restoration of skilled locomotor movements. I discuss how this approach is now being applied to a C4 contusion rat model.
As most spinal cord injuries （SCIs） are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal motor circuits. Among the pathways, the corticospinal tract （CST） is most associated with skilled voluntary functions in humans and many animals. CST loss, whether at its origin in the motor cortex or in the white matter tracts subcortically and in the spinal cord, leads to movement impairments and paraly- sis. To restore motor function after injury will require repair of the damaged CST. In this review, I discuss how knowledge of activity-dependent development of the CST--which establishes connectional speci- ficity through axon pruning, axon outgrowth, and synaptic competition among CST terminals--informed a novel activity-based therapy for promoting sprouting of spared CST axons after injur in mature animals. This therapy, which comprises motor cortex electrical stimulation with and without concurrent trans-spi- nal direct current stimulation, leads to an increase in the gray matter axon length of spared CST axons in the rat spinal cord and, after a pyramidal tract lesion, restoration of skilled locomotor movements. I discuss how this approach is now being applied to a C4 contusion rat model.
基金
Support provided by grants from the National Institutes of Health R01NS064004
the New York State Department of Health Spinal Cord Injury Board C30606GG,C30835GG
