Traumatic brain injury (TBI) patients would benefit from the identification of reliable
biomarkers to predict outcomes and treatment strategies. In our study, cerebrospinal fluid (CSF) from patients with severe TBI was evaluated for
oxidant stress-mediated damage progression after hospital admission and subsequent
ventriculostomy placement. Interestingly, substantial levels of
peroxiredoxin VI (Prdx6), a major
antioxidant enzyme normally found in astrocytes, were detected in CSF from control and TBI patients and were not associated with blood contamination. Functionally, Prdx6 and its associated binding partner
glutathione S-transferase Pi (GSTP1-1, also detected in CSF) act in tandem to detoxify lipid peroxidation damage to membranes. We found Prdx6 was fully active in CSF of control patients but becomes significantly inactivated (oxidized) in TBI. Furthermore, significant and progressive oxidation of "buried"
protein thiols in CSF of TBI patients (compared to those of nontrauma controls) was detected over a 24-h period after hospital admission, with increased oxidation correlating with severity of
trauma. Conversely, recovery of Prdx6 activity after 24h indicated more favorable patient outcome. Not only is this the first report of an extracellular form of Prdx6 but also the first report of its detection at a substantial level in CSF. Taken together, our data suggest a meaningful correlation between TBI-initiated oxidation of Prdx6, its specific
phospholipid hydroperoxide peroxidase activity, and severity of
trauma outcome. Consequently, we propose that Prdx6 redox status detection has the potential to be a
biomarker for TBI outcome and a future
indicator of therapeutic efficacy.