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Project Title:
Therapeutic Hypothermia and Nitrosative Stress After Severe Traumatic Brain Injury
Funding Agency:
Laerdal Medical Foundation
Total Project Period:
Jan 01, 2003 – Jun 30, 2004
Principal Investigator:
Hulya Bayir, MD
Co-Investigator(s):
Valerian Kagan, P. David Adelson
Project Summary:
Traumatic brain injury (TBI) sets into motion a deleterious secondary cascade of biochemical and molecular events. Oxidative damage plays a key role in secondary damage after TBI. Oxidative damage results from production of reactive oxygen (oxidative stress) and nitrogen species (nitrosative stress). Our recent report shows attenuation of oxidative stress by hypothermia after severe TBI in infants and children, suggesting that hypothermia is beneficial. In contrast to oxidative stress, which contributes to secondary damage, nitrosative stress may confer both detrimental and beneficial effects. To date there has been no experimental or clinical study addressing the effect of therapeutic hypothermia on nitrosative stress after TBI. Therefore we hypothesize that hypothermia will attenuate nitrosative stress after severe TBI in infants and children. Using an IRB approved protocol, ventricular CSF samples (n = 120) from 30 infants and children (15 normothermia 15 treated with hypothermia) will be collected within the first 8 h and for the initial 4 d then immediately frozen until analysis. This will allow assessment during hypothermia (48 h) and re-warming. CSF will also be obtained from age-matched controls (n=15, children who underwent lumbar puncture to rule out meningitis [confirmed negative cultures and no pleocytosis]) for analysis. Nitrotyrosine and S-nitrosothiols will be quantified by ELISA and fluorescent assay respectively. Time course and association of CSF nitrotyrosine and S-nitrosothiol levels with demographic and clinical parameters (age, gender, mechanism of injury [accidental vs. abuse], admission GCS, outcome, head CT scan, ICP, CPP) will also be determined.
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