Harnessing activity-dependent plasticity to repair the damaged corticospinal tract in an animal model of cerebral palsy.

Overview

The corticospinal tract (CST) is the principal motor control pathway for skilled movements. It has a protracted postnatal development, creating a protracted period of vulnerability to perinatal brain and spinal cord injury. Research has shown that the motor signs in cerebral palsy (CP) reflect the loss of CST connections as well as development of abnormal motor systems connections, especially between the developing CST and spinal motor circuits. In this paper, we discuss a feline model of CP that we have developed. The animals develop a pattern of abnormal CST connections that is remarkably similar to that seen in hemiplegic CP and visuomotor impairments. Using this model we devised neural activity-based therapeutic approaches to repair the abnormal CST connections and restore normal skilled movement control. Our studies stress that more active CST connections are better able to maintain strong synaptic connections with spinal motor circuits. We propose that perinatal trauma initiates a vicious cycle in which CST axons that are spared after an injury are at a disadvantage for maintaining spinal connections, leading to further reductions in connections and motor signs. If this is so, targeted activation of the spared CST might interrupt this process and lead to functional improvement.