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 goal of the current research proposal is to demonstrate that the exogenous administration of these trophic factors will enhance dendritic growth, synaptic efficacy, and inhibit calpain- mediated axonal injury to prevent chronic cognitive deficits. These studies are very relevant to public health because it 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS053651-05
Application #
7758770
Study Section
NST-2 Subcommittee (NST)
Program Officer
Hicks, Ramona R
Project Start
2006-03-06
Project End
2011-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
5
Fiscal Year
2010
Total Cost
$170,166
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Dileonardi, Ann Mae; Huh, Jimmy W; Raghupathi, Ramesh (2012) Differential effects of FK506 on structural and functional axonal deficits after diffuse brain injury in the immature rat. J Neuropathol Exp Neurol 71:959-72
Huh, Jimmy W; Widing, Ashley G; Raghupathi, Ramesh (2011) Differential effects of injury severity on cognition and cellular pathology after contusive brain trauma in the immature rat. J Neurotrauma 28:245-57
Avery, Robert A; Shah, Samir S; Licht, Daniel J et al. (2010) Reference range for cerebrospinal fluid opening pressure in children. N Engl J Med 363:891-3
Huh, Jimmy W; Raghupathi, Ramesh (2009) New concepts in treatment of pediatric traumatic brain injury. Anesthesiol Clin 27:213-40
DiLeonardi, Ann Mae; Huh, Jimmy W; Raghupathi, Ramesh (2009) Impaired axonal transport and neurofilament compaction occur in separate populations of injured axons following diffuse brain injury in the immature rat. Brain Res 1263:174-82
Huh, Jimmy W; Widing, Ashley G; Raghupathi, Ramesh (2008) Midline brain injury in the immature rat induces sustained cognitive deficits, bihemispheric axonal injury and neurodegeneration. Exp Neurol 213:84-92
Abend, Nicholas S; Huh, Jimmy W; Helfaer, Mark A et al. (2008) Anticonvulsant medications in the pediatric emergency room and intensive care unit. Pediatr Emerg Care 24:705-18;quiz 719-21
Huh, Jimmy W; Raghupathi, Ramesh (2007) Chronic cognitive deficits and long-term histopathological alterations following contusive brain injury in the immature rat. J Neurotrauma 24:1460-74
Huh, Jimmy W; Widing, Ashley G; Raghupathi, Ramesh (2007) Basic science;repetitive mild non-contusive brain trauma in immature rats exacerbates traumatic axonal injury and axonal calpain activation: a preliminary report. J Neurotrauma 24:15-27
Raghupathi, Ramesh; Huh, Jimmy W (2007) Diffuse brain injury in the immature rat: evidence for an age-at-injury effect on cognitive function and histopathologic damage. J Neurotrauma 24:1596-608