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InterstitialF2-Isoprostane8-Iso-PGF2αAs aBiomarker ofOxidative Stressafter Severe HumanTraumatic BrainInjury Fredrik ClausenNiklas MarklundAnders Lewén2011 год

Interstitial F2-Isoprostane 8-Iso-PGF2αAs a Biomarker of Oxidative Stress after Severe Human Traumatic Brain Injury
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Аннотация: Oxidative stress is a major contributor to the secondary injury process after experimental traumatic brain injury (TBI). The importance of oxidative stress in the pathobiology of human TBI is largely unknown. The F2-isoprostane 8-iso-prostaglandin F2α (8-iso-PGF2α), synthesized in vivo through non-enzymatic free radical catalyzed peroxidation of arachidonic acid, is a widely used biomarker of oxidative stress in multiple disease states, including TBI and cerebral ischemia/reperfusion. Our hypothesis is that harvesting of biomarkers directly in the injured brain by cerebral microdialysis (MD) is advantageous because of its high spatial and temporal resolution compared to blood or cerebrospinal fluid sampling. The aim of this study was to test the feasibility of measuring 8-iso-PGF2α in MD, ventricular cerebrospinal fluid (vCSF), and plasma samples collected from patients with severe TBI, and to compare the MD signals with MD-glycerol, implicated as a biomarker of oxidative stress, as well as MD-glutamate, a biomarker of excitotoxicity. Six patients (4 men, 2 women) were included in the study, three of whom had a focal/mixed TBI, and three a diffuse axonal injury (DAI). Following the bedside analysis of routine MD biomarkers (glucose, lactate:pyruvate ratio, glycerol, and glutamate), two 12-h MD samples per day were used to analyze 8-iso-PGF2α from 24 h up to 8 days post-injury. The interstitial levels of 8-iso-PGF2α were markedly higher than the levels obtained from plasma and vCSF (p<0.05), supporting our hypothesis. The MD-8-iso-PGF2α levels correlated strongly (p<0.05) with MD-glycerol and MD-glutamate, which are widely used biomarkers of membrane phospholipid degradation/oxidative stress and excitotoxicity, respectively. This study demonstrates the feasibility of analyzing 8-iso-PGF2α in MD samples from the human brain. Our results support a close relationship between oxidative stress and excitotoxicity following human TBI. MD-8-iso-PGF2α in combination with MD-glycerol may be useful biomarkers of oxidative stress in the neurointensive care setting.
Год издания: 2011
Авторы: Fredrik Clausen, Niklas Marklund, Anders Lewén, Per Enblad, Samar Basu, Lars Hillered
Издательство: Mary Ann Liebert, Inc.
Источник: Journal of Neurotrauma
Ключевые слова: Traumatic Brain Injury and Neurovascular Disturbances, Eicosanoids and Hypertension Pharmacology, Heme Oxygenase-1 and Carbon Monoxide
Другие ссылки: Journal of Neurotrauma (HTML)
PubMed (HTML)