Nitrotyrosine As an Oxidative Stress Marker: Evidence for Involvement in Neurologic Outcome in Human Traumatic Brain Injury

Background: Oxidative stress has been indicated as a mechanism of secondary neuronal injury in traumatic brain injury (TBI). Nitrotyrosine in the cerebrospinal fluid (CSF) may be an in vivo marker of oxidative nitric oxide damage. We tested the hypothesis that increased levels of nitrotyrosine correlate with poor neurologic outcomes in patients with TBI and attempted to identify the source of increased CSF nitrotyrosine.

Methods: This institutional-review-board-approved study included 10 adults with severe closed TBI (Glasgow Coma Scale score <8) and no documented hypoxic brain injury. These patients underwent routine evaluation and, when indicated, placement of an intraventricular catheter. CSF samples (n = 27) were collected 2 to 72 hours after TBI and were also obtained from four healthy individuals. Nitrotyrosine levels were measured, and immunohistochemistry was performed. Neurologic follow-up extended to 1 month after injury.

Results: Nitrotyrosine was not detected in the control samples but was detected in 13 CSF samples from 7 TBI patients (range, 22.4-97.6 nM/mL). Seven patients had poor outcomes, and, in each, nitrotyrosine was detected. Nitrotyrosine immunoreactivity was detected in neurons and glia and confirmed in brain homogenate.

Conclusion: Oxidative stress contributes to secondary brain injury in patients with TBI. Poor neurologic outcome is associated with increased levels of nitrotyrosine in the CSF. Identifying patients or the stage at which oxidative stress is more active using CSF markers of oxidative injury may help in the development of more targeted treatments.