Assessment of Antioxidant Reserves and Oxidative Stress in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children

Bayır, Hülya; Kagan, Valerian E.; Tyurina, Yulia Y.; Tyurin, Vladimir A.; Ruppel, Randall A.; Adelson, P. David; Graham, Steven H.; Janesko, Keri L.; Clark, Robert S. B.; Kochanek, Patrick M.

doi:10.1203/00006450-200205000-00005

Cited by 224 publications

(158 citation statements)

References 51 publications

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“…12,13,23 Cerebrospinal fluid F2-isoprostanes are a unique series of prostaglandin-like compounds formed in vivo from the free radical-catalyzed peroxidation of arachidonic acid and have been used to assess peroxidation in patients with severe TBI. 3,4,17,35 Glycerol is an end product of phospholipid degradation in neural tissue cell membranes and is a marker of cell damage whether caused by O 2 toxicity via free radical formation and lipid peroxidation or secondarily from ischemia. 16,19,32 Levels of CSF F2-isoprostanes as well as microdialysate glycerol were significantly decreased following combined HBO 2 /NBH treatment.…”

Section: Oxygen Toxicitymentioning

confidence: 99%

A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury

Rockswold

Zaun

et al. 2013

JNS

129

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T he enormous negative social and economic impact of TBI throughout the world cannot be overemphasized. The major issue is premature death and disability both in civilian and military populations. Conservative estimates of the prevalence of long-term disability due to TBI in the United States are well over 3 million people. The economic toll of TBI exceeds $60 billion per year. 18 Our previous investigations of HBO 2 Object. Preclinical and clinical investigations indicate that the positive effect of hyperbaric oxygen (HBO 2 ) for severe traumatic brain injury (TBI) occurs after rather than during treatment. The brain appears better able to use baseline O 2 levels following HBO 2 treatments. In this study, the authors evaluate the combination of HBO 2 and normobaric hyperoxia (NBH) as a single treatment.Methods. Forty-two patients who sustained severe TBI (mean Glasgow Coma Scale [GCS] score 5.7) were prospectively randomized within 24 hours of injury to either: 1) combined HBO 2 /NBH (60 minutes of HBO 2 at 1.5 atmospheres absolute [ATA] followed by NBH, 3 hours of 100% fraction of inspired oxygen [FiO 2 ] at 1.0 ATA) or 2) control, standard care. Treatments occurred once every 24 hours for 3 consecutive days. Intracranial pressure, surrogate markers for cerebral metabolism, and O 2 toxicity were monitored. Clinical outcome was assessed at 6 months using the sliding dichotomized Glasgow Outcome Scale (GOS) score. Mixedeffects linear modeling was used to statistically test differences between the treatment and control groups. Functional outcome and mortality rates were compared using chi-square tests.Results. There were no significant differences in demographic characteristics between the 2 groups. In comparison with values in the control group, brain tissue partial pressure of O 2 (PO 2 ) levels were significantly increased during and following combined HBO 2 /NBH treatments in both the noninjured and pericontusional brain (p < 0.0001). Microdialysate lactate/pyruvate ratios were significantly decreased in the noninjured brain in the combined HBO 2 /NBH group as compared with controls (p < 0.0078). The combined HBO 2 /NBH group's intracranial pressure values were significantly lower than those of the control group during treatment, and the improvement continued until the next treatment session (p < 0.0006). The combined HBO 2 /NBH group's levels of microdialysate glycerol were significantly lower than those of the control group in both noninjured and pericontusional brain (p < 0.001). The combined HBO 2 /NBH group's level of CSF F2-isoprostane was decreased at 6 hours after treatment as compared with that of controls, but the difference did not quite reach statistical significance (p = 0.0692). There was an absolute 26% reduction in mortality for the combined HBO 2 /NBH group (p = 0.048) and an absolute 36% improvement in favorable outcome using the sliding dichotomized GOS (p = 0.024) as compared with the control group.Conclusions. In this Phase II clinical trial, in comparison with standard care (control t...

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Section: Oxygen Toxicitymentioning

confidence: 99%

A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury

Rockswold

Zaun

et al. 2013

JNS

129

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“…69 This vulnerability is further compounded in the immature brain by a reduced antioxidant reserve. Bayir et al 70 assessed measures of oxidative stress and total antioxidant reserve in the cerebrospinal fluid of head-injured infants and children and demonstrated a reduction in total antioxidant reserve compared to controls as well as a depletion of the antioxidant compounds ascorbic acid and glutathione. Such findings may be due to the regulation of antioxidant enzymes during brain development and maturation.…”

Section: Oxidative Damagementioning

confidence: 99%

Traumatic injury to the immature brain: Inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets

Potts

Koh

Whetstone

et al. 2006

NeuroRX

143

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Summary: Traumatic brain injury (TBI) is the leading cause of morbidity and mortality among children and both clinical and experimental data reveal that the immature brain is unique in its response and vulnerability to TBI compared to the adult brain. Current therapies for pediatric TBI focus on physiologic derangements and are based primarily on adult data. However, it is now evident that secondary biochemical perturbations play an important role in the pathobiology of pediatric TBI and may provide specific therapeutic targets for the treatment of the head-injured child. In this review, we discuss three specific components of the secondary pathogenesis of pediatric TBIinflammation, oxidative injury, and iron-induced damage -and potential therapeutic strategies associated with each. The inflammatory response in the immature brain is more robust than in the adult and characterized by greater disruption of the blood-brain barrier and elaboration of cytokines. The immature brain also has a muted response to oxidative stress compared to the adult due to inadequate expression of certain antioxidant molecules. In addition, the developing brain is less able to detoxify free iron after TBI-induced hemorrhage and cell death. These processes thus provide potential therapeutic targets that may be tailored to pediatric TBI, including anti-inflammatory agents such as minocycline, antioxidants such as glutathione peroxidase, and the iron chelator deferoxamine.

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“…Fluorescence Assay of GSH and Protein-SH-The concentrations of GSH and protein-SH were determined using ThioGlo-1, a maleimide reagent that produces a highly fluorescent product upon its reaction with sulfhydryl groups (20), modified for use in culture and brain tissue. A standard curve was established using 0.04 -4 M GSH in 50 mM Na 2 PO 4 buffer, pH 7.4, containing 10 M Thio-Glo-1.…”

mentioning

confidence: 99%

Innate Gender-based Proclivity in Response to Cytotoxicity and Programmed Cell Death Pathway

Du¹,

Bayır²,

Lai³

et al. 2004

Journal of Biological Chemistry

Self Cite

328

279

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Many central nervous system (CNS) diseases display sexual dimorphism. Exposure to circulating sex steroids is felt to be a chief contributor to this phenomenon; however, CNS diseases of childhood and the elderly also demonstrate gender predominance and/or a sexually dimorphic response to therapies. Here we show that XY and XX neurons cultured separately are differentially susceptible to various cytotoxic agents and treatments. XY neurons were more sensitive to nitrosative stress and excitotoxicity versus XX neurons. In contrast, XX neurons were more sensitive to etoposide-and staurosporine-induced apoptosis versus XY neurons. The responses to specific therapies were also sexually dimorphic. Moreover, gender proclivity in programmed cell death pathway was observed. After cytotoxic challenge, programmed cell death proceeded predominately via an apoptosis-inducing factor-dependent pathway in XY neurons versus a cytochrome c-dependent pathway in XX neurons. This gender-dependent susceptibility is related to the incapacity of XY neurons to maintain intracellular levels of reduced glutathione. In vivo studies further demonstrated an incapacity for male, but not female, 17-day-old rats to maintain reduced glutathione levels within cerebral cortex acutely after an 8-min asphyxial cardiac arrest. This gender difference in sensitivity to cytotoxic agents may be generalized to nonneuronal cells, as splenocytes from male and female 16 -18-day-old rats show similar gender-dependent responses to nitrosative stress and staurosporine-induced apoptosis. These data support gender stratification in the evaluation of mechanisms and treatment of CNS disease, particularly those where glutathione may play a role in detoxification, such as Parkinson's disease, traumatic brain injury, and conditions producing cerebral ischemia, and may apply to non-CNS diseases as well.

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Assessment of Antioxidant Reserves and Oxidative Stress in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children

Cited by 224 publications

References 51 publications

A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury

A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury

Traumatic injury to the immature brain: Inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets

Innate Gender-based Proclivity in Response to Cytotoxicity and Programmed Cell Death Pathway

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