Funding outcome

Cerebral palsy (CP) is caused by damage to the brain near the time of birth and is the leading cause of permanent motor and sensory impairment in children. In CP, weak voluntary movements are hampered by excessive involuntary, uncontrolled movements termed 'spasticity'. Despite the severity and high incidence of CP (~ 1 in every 400 live births), there has been little advancement in treating the underlying causes of spasticity, which often require multiple orthopedics surgeries, botulinum toxin and bracing to control. We will use a newly developed animal model of CP, where a rabbit foetus is exposed to reduced levels of oxygen, to measure how neurons in the spinal cord that control the muscles of the body (termed motoneurons), contribute to the spasticity that manifests in these animals. We will also perform parallel experiments in children with CP where we can measure the activity of spinal motoneurons using newly developed muscle recording and data analysis techniques. These combined animal and human studies will allow us to directly measure perturbations in the normal development of spinal motoneurons and neuronal circuits, while relating these cellular changes to spastic motor behaviors. These findings will determine if enhanced excitability in spinal motoneurons, in addition to reduced damping of their activity by sensory inputs, could be targets for therapeutic interventions. Once we understand what is driving the abnormal excitability of spinal motoneurons, we can then develop both drug and rehabilitation techniques to help reduce it or optimally, to help prevent spasticity from developing in the first place. To this end, we will measure spinal neuronal excitability before spasticity fully develops in both the rabbit (neo-natal to maturity) and in children (4 to 18 years of age). In summary, this project investigates previously under-characterized spinal mechanisms of motor impairment in CP development, and can open new therapeutic avenues.