The candidate's goal is to become an independent clinician-scientist in pediatric traumatic brain injury (TBI) by training with an outstanding group of mentors and an advisory committee from the University of Pennsylvania and Drexel University College of Medicine who are authorities in the field of pediatric TBI research. The environment at Penn and Drexel are rich with resources and personnel so that this junior investigator will become more facile with laboratory skills, scientific writing, research design and experimental methodology outlined in this research proposal. Dr. Huh is a pediatric critical care physician at Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, who takes care of children with traumatic brain injury (TBI). Despite the fact that TBI is the number one cause of acquired disability and death in children, only supportive care can be provided in the acute setting. Head-injured children are often left with chronic learning (cognitive) deficits. Following TBI, the brain appears to transiently increase endogenous molecules called neurotrophic factors such as Insulin-like growth factor I (IGF-I) and Nerve growth factor (NGF), whose expression is highest in the pediatric brain and important for recovery by promoting dendritic growth, synaptic efficacy, and inhibiting calpains, proteases implicated in traumatic axonal damage. Using a clinically relevant model of closed head injury in pediatric rats, the goals of this research proposal are to demonstrate that the exogenous administration of these trophic factors can enhance dendritic growth and synaptic efficacy, and inhibit calpain-mediated axonal injury to prevent chronic cognitive deficits. These studies are very relevant to public health because they will provide the rationale for future investigations for the candidate to develop novel translational therapies to inhibit cellular processes associated with chronic behavioral deficits and to enhance brain recovery in head-injured children. ? ?
