부산대학교 도서관

Studies in experimental traumatic brain injury (TBI) support a key role for oxidative stress. The degree of oxidative injury in clinical TBI, however, remains to be defined. We assessed antioxidant defenses and oxidative stress in pediatric TBI by applying a comprehensive battery of assays to cerebrospinal fluid samples. Using a protocol approved by our institutional review board, 87 cerebrospinal fluid samples from 11 infants and children with severe TBI (Glasgow Coma Scale score ≤8) and 8 controls were studied. Cerebrospinal fluid was drained as standard care after TBI. CSF was assessed on d 1, 2, and 5–7 after ventricular drain placement. Biochemical markers of oxidative stress included F2-isoprostane and protein sulfhydryl (detected by ELISA and fluorescence assay, respectively). Antioxidant defenses were measured by determination of total antioxidant reserve (viachemiluminescence assay), and ascorbate (viaHPLC) and glutathione (viafluorescence assay) concentrations. Free radical production (ascorbate radical) was assessed by electron paramagnetic resonance spectroscopy. F2-isoprostane was markedly increased versuscontrol, maximal on d 1 (93.8 ± 30.8 pg/mL versus7.6 ± 5.1 pg/mL, p< 0.05). Total antioxidant reserve was reduced versuscontrol. Reduction was maximal on d 5–7 (81.8 ± 3.7 M versus178.9 ± 2.2 M, p< 0.05). Ascorbate was remarkably reduced (53.8 ± 8 M versus163.8 ± 21 M on d 1, p< 0.05). Ascorbate depletion was likely associated with its free radical oxidation, as evidenced by electron paramagnetic resonance spectroscopy. Glutathione levels increased on d 1, then decreased versuscontrol (0.19 ± 0.05 M versus1.2 ± 0.16 M, p< 0.05). This is the first comprehensive study of antioxidant reserve and oxidative injury in clinical TBI. Progressive compromise of antioxidant defenses and evidence of free radical–mediated lipid peroxidation are noted. These markers could be used to monitor antioxidant strategies in clinical trials.