Funding Agency:

National Institutes of Health, National Institute of Neurological Disorders and Stroke (Grant No. R01 NS069249)

Total Project Period:

09/30/09 – 06/30/14

Total Project Award:

$2,814,385

Principal Investigator:

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

Co-Investigators:

C. Edward Dixon PhD; Hulya Bayir, MD, Samuel Poloyac, PhD, Stephen Wisniewski, PhD

Project Summary:

Our hypothesis is that combinational strategies that include therapies that overcome membrane transport barriers will synergistically improve bioavailability and efficacy of both clinically used and novel therapies after TBI.

Specific aims are to define the capacity of the combination of a membrane transporter inhibitor, probenecid, and a cysteine-donor antioxidant, NAC, to synergistically reduce efflux of GSH, reduce oxidative stress, and improve neurological outcome in neurons after stretch-induced trauma in vitro and in mice after TBI in vivo; and to define the capacity of the combination of probenecid and NAC to safely and synergistically preserve levels of GSH and reduce oxidative stress in children with severe TBI.