Funding Agency:

National Institutes of Health, National Institute of Neurological Disorders and Stroke (Grant No. R01 NS038620)

Total Project Period:

2/1/03 - 1/31/09

Total Project Award:

$1,842,781

Principal Investigator:

Robert S.B. Clark, MD (Critical Care Medicine)

Co-Investigators:

C. Edward Dixon, PhD, Patrick M. Kochanek, PhD (Critical Care Medicine); Jun Chen, MD (Neurology); Xiaopeng, Zhang (Anesthesia/Critical Care Medicine)

Project Summary:

It is established that programmed-cell death contributes to secondary neuronal death after traumatic brain injury (TBI) in experimental models and in humans; however, recent data suggest that multiple cell death pathways exist. Specifically, an alternate/additional pathway of cell death involving the mitochondrial protein apoptosis-inducing factor (AIF) that produces large scale DNA fragmentation and cell death that it is inhibited by bcl-2 and hsp70, but not by caspase inhibitors, appears to contribute to neuronal cell death in models of nitrosative stress in vitro, and after TBI in vivo. The objective of this research is to determine whether divergent and parallel cell death pathways contribute to neuronal demise after acute brain injury.