Role of neurotrophins in spinal plasticity and locomotion.

Synaptic transmission through descending motor pathways to lumbar motoneurons and then to leg muscles is essential for walking in humans and rats. Spinal cord injury (SCI), even when incomplete, results in diminished transmission to motoneurons and very limited recovery of motor function. Neurotrophins have emerged as essential molecules known to promote cell survival and support anatomical reorganization in damaged spinal cord. This review will summarize the evidence implicating the role of neurotrophins in synaptic plasticity in both undamaged and damaged spinal cord, with special emphasis on the potential for neurotrophins to strengthen synaptic connections to motoneurons in support of the application of neurotrophins for recovery of locomotor function after SCI. An important consideration related to therapeutic use of neurotrophins is the successful delivery of these molecules. Prolonged delivery of neurotrophins to the spinal cord of adult mammals has recently become possible through advances in biotechnology. Fibroblasts engineered to secrete neurotrophins and gene transfer of neurotrophins via recombinant viral vectors are among the most promising therapeutic transgene delivery systems for safe and effective neurotrophin delivery. Administration of neurotrophins to the spinal cord using these delivery systems was found to enhance both anatomical and synaptic plasticity and improve functional recovery after SCI. The findings summarized here indicate that neurotrophins have translational research potential for SCI repair, most likely as an essential component of combination therapy.