Funding Agency:

National Institutes of Health, National Institute of Neurological Disorders and Stroke (NINDS) (Grant No. R01 NS042648)

Total Project Period:

2/15/2004 - 1/31/09

Total Project Award:

$1,373,913

Principal Investigator:

Larry W. Jenkins, PhD

Co-Investigators:

C. Edward Dixon, PhD; Patrick Kochanek, MD (Critical Care Medicine)

Project Summary:

The protein kinase B (PKB) and protein kinase C (PKC) enzyme families participate in many cellular functions including protein syntheseis. Catabolism, weight loss, and impaired developmental body and brain weight gains have been documented after pediatric traumatic brain injury (TBI). Hypothermia treatment has been shown to improve developmental brain weight in specific brain regions important in cognitive function such as the hippocampus and spatial memory after injury. However, recent study has shown that pediatric TBI alters hippocampal protein synthesis and while hypothermia improves protein synthesis recovery after cerebral ischemia, this has not been examined after TBI in either adult or immature animals. Hypothermia is a unique modulator of protein synthesis in that it depresses overall protein synthesis but selectively increases cap-independent synthesis of stress proteins via cold shock stress. This study hypothesizes that post-injury hypothermia promotes functional recovery following pediatric TBI not primarily due to inhibition of excitotoxic glutamate release (which has already occurred) but by activating beneficial stress related IRES protein synthesis causing cold stress induced tolerance to secondary injury processes.