title: Interstitial F(2)-isoprostane 8-iso-PGF(2α) as a biomarker of oxidative stress after severe human traumatic brain injury.
abstract: 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 F(2)-isoprostane 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)), 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-PGF(2α) 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-PGF(2α) from 24 h up to 8 days post-injury. The interstitial levels of 8-iso-PGF(2α) were markedly higher than the levels obtained from plasma and vCSF (p<0.05), supporting our hypothesis. The MD-8-iso-PGF(2α) 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-PGF(2α) in MD samples from the human brain. Our results support a close relationship between oxidative stress and excitotoxicity following human TBI. MD-8-iso-PGF(2α) in combination with MD-glycerol may be useful biomarkers of oxidative stress in the neurointensive care setting.
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala University Hospital, Uppsala, Sweden. Fredrik.clausen@neuro.uu.se
authors.forename: Fredrik
authors.initials: F
authors.lastname: Clausen
authors.forename: Niklas
authors.initials: N
authors.lastname: Marklund
authors.forename: Anders
authors.initials: A
authors.lastname: Lewén
authors.forename: Per
authors.initials: P
authors.lastname: Enblad
authors.forename: Samar
authors.initials: S
authors.lastname: Basu
authors.forename: Lars
authors.initials: L
authors.lastname: Hillered
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost