title: Therapeutic hypothermia preserves antioxidant defenses after severe traumatic brain injury in infants and children.
abstract: OBJECTIVE
  Oxidative stress contributes to secondary damage after traumatic brain injury (TBI). Hypothermia decreases endogenous antioxidant consumption and lipid peroxidation after experimental cerebral injury. Our objective was to determine the effect of therapeutic hypothermia on oxidative damage after severe TBI in infants and children randomized to moderate hypothermia vs. normothermia.
  
  
  METHODS
  Prospective randomized controlled study.
  
  
  METHODS
  Pediatric intensive care unit of Pittsburgh Children's Hospital.
  
  
  METHODS
  The study included 28 patients.
  
  
  RESULTS
  We compared the effects of hypothermia (32 degrees C-33 degrees C) vs. normothermia in patients treated in a single center involved in a multicentered randomized controlled trial of hypothermia in severe pediatric TBI (Glasgow Coma Scale score <or=8). The patients randomized to hypothermia (n = 13) were cooled to target temperature within approximately 6 to 24 hours for 48 hours and then rewarmed. Antioxidant status was assessed by measurements of total antioxidant reserve and glutathione. Protein oxidation and lipid peroxidation were assessed by measurements of protein thiols and F2-isoprostane, respectively, in ventricular cerebrospinal fluid (CSF) samples (n = 76) obtained on day 1-3 after injury. The association between Glasgow Coma Scale score, age, gender, treatment, temperature, time after injury, and CSF antioxidant reserve, glutathione, protein-thiol, F2-isoprostane levels were assessed by bivariate and multiple regression models. Demographic and clinical characteristics were similar between the two treatment groups. Mechanism of injury included both accidental injury and nonaccidental injury. Multiple regression models revealed preservation of CSF antioxidant reserve by hypothermia (p = 0.001). Similarly, a multiple regression model showed that glutathione levels were inversely associated with patient temperature at the time of sampling (p = 0.002). F2-isoprostane levels peaked on day 1 after injury and were progressively decreased thereafter. Although F2-isoprostane levels were approximately three-fold lower in patients randomized to hypothermia vs. normothermia, this difference was not statistically significant.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study demonstrating that hypothermia attenuates oxidative stress after severe TBI in infants and children. Our data also support the concept that CSF represents a valuable tool for monitoring treatment effects on oxidative stress after TBI.
authors.affiliation: Safar Center for Resuscitation Research, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Hülya
authors.initials: H
authors.lastname: Bayir
authors.forename: P David
authors.initials: PD
authors.lastname: Adelson
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wisniewski
authors.forename: Paul
authors.initials: P
authors.lastname: Shore
authors.forename: YiChen
authors.initials: Y
authors.lastname: Lai
authors.forename: Danielle
authors.initials: D
authors.lastname: Brown
authors.forename: Keri L
authors.initials: KL
authors.lastname: Janesko-Feldman
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D007223:Infant; D008297:Male; D018384:Oxidative Stress; D011446:Prospective Studies
chemical_list: D000975:Antioxidants