Abstract P117: Oxidant Injury Occurs Early After Traumatic Brain Injury in Humans: Cerebrospinal Fluid Isofuran and F2-Isoprostane Are Sensitive Markers of Oxidant Injury
Background: Traumatic brain injury (TBI) causes 50,000 deaths/year. Although recent studies indicate that oxidant injury may be deleterious, progress in this area has been hampered by lack of adequate biomarkers for oxidant injury. F2-isoprostane (IsoP) and Isofuran (IsoF) are stable peroxidation products of cell membrane phospholipids that increase dramatically during oxidant injury. Formation of IsoF is favored in the presence of oxygen while IsoP is an indicator of a low oxygen tension environment as occurs during ischemia. We showed previously in an animal model that cerebrospinal fluid (CSF) IsoP increases significantly within 30 minutes of traumatic brain injury (TBI).
Objective: To determine CSF IsoP and IsoF levels in patients with TBI.
Methods: This study was approved by our IRB. Patients who suffered severe TBI, had a GCS of 3– 8, and a clinically-indicated ventriculostomy were enrolled (N=10). Serial CSF was collected for measurements beginning as early as 8 hours after TBI. IsoP and IsoF levels were measured using gas chromatography and mass spectroscopy.
Results: IsoP and IsoF levels were 3- to 5-times higher than normal (<4 pg/mL) in the first specimens obtained (8 to 16 hours after TBI). During the first 24 hours after TBI, mean (±SD) IsoP was 16.0±8.6 pg/mL (range 6 –31) and mean IsoF was 21.1±16.8 pg/mL (range 14 – 69). In the first 24 hours post-injury, there was a strong trend toward an increased CSF IsoF to IsoP ratio in patients with good prognosis. An IsoF/IsoP ratio of <1 was associated with mortality.
Conclusion: CSF IsoP and IsoF levels were much higher than normal within 8 hours in patients suffering severe TBI indicating that oxidant injury occurs rapidly after TBI. In addition, IsoF to IsoP ratios may have prognostic value.