This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cerebral Palsy (CP) is the most common disabling neurological disease in children. The incidence rate of CP is rising in developed countries. Our long-term goal is to understand the mechanism leading to the motor system dysfunction in children with CP, as the disease affects almost exclusively the motor system of affected children. Patients with adult-type diseases such as stroke share common features with CP and are known to have abnormalities at their neuromuscular junction (NMJ). Encouraged by these findings in adults coupled with the need to understand the NMJs in CP, which are critical for motor system function, we formulated the following central hypothesis: Children with CP have inherent abnormalities present in their NMJs that contribute to the motor-system dysfunction seen during their lifetimes. In order to test this hypothesis we developed three specific aims: 1) To examine and describe the neuromuscular junction in children with cerebral palsy with respect to their structure and function; 2) To explore associations that exist between the abnormalities evident in the neuromuscular junction and clinical features of cerebral palsy, most notably, spasticity; 3) To study animal models of cerebral palsy to better enable us to understand the structural and functional characteristics of the peripheral nervous system in cerebral palsy.
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