Strategies for axonal repair in central nervous system diseases

Significant functional recovery after spinal cord injury can be observed in rodents, in spite of the presence of extensive irreversible structural damage. One potential mechanism for functional regeneration of the corticospinal tract may involve the formation of new spinal circuits remote from the lesion that allow the lesion site to be by-passed and contact re-established with the original targets of the transected axons. In both traumatic and inflammatory lesions of the spinal cord, transection at the thoracic level is followed by extensive collateral sprouting at higher levels of the spinal cord. These collaterals can make contact with long propriospinal neurones in the cervical cord, which project to the lumbar ventral horn via the ventral funiculus. These new connections can serve as a ‘bridge’ to reconnect the corticospinal neurone to its target anterior horn cell. The integrity of this circuitry has been demonstrated by retrograde tracing with pseudorabies virus. Recuperation of electromyographic activity following stimulation of the motor cortex indicates that these new spinal circuits are functionally active. Such remodelling of spinal circuitry following spinal injury may play an important role in determining the extent of functional recovery.