Normoxic ventilatory resuscitation following controlled cortical impact reduces peroxynitrite-mediated protein nitration in the hippocampus.

Abstract

Ventilatory resuscitation with 100% O2 after severe traumatic brain injury (TBI) raises concerns about the increased production of reactive oxygen species (ROS). The product of peroxynitrite-meditated tyrosine residue nitration, 3-nitrotyrosine (3-NT), is a marker for oxidative damage to proteins. The authors hypothesized that posttraumatic resuscitation with hyperoxia (100% fraction of inspired oxygen [FiO2] concentration) results in increased ROS-induced damage to proteins compared with resuscitation using normoxia (21% FiO2 concentration). Male Sprague-Dawley rats underwent controlled cortical impact (CCI) injury and resuscitation with either normoxic or hyperoxic ventilation for 1 hour (5 rats per group). Twenty-four hours after injury, rat hippocampi were evaluated using 3-NT immunostaining. In a second experiment, animals similarly underwent CCI injury and normoxic or hyperoxic ventilation for 1 hour (4 rats per group). One week after injury, neuronal counts were performed after neuronal nuclei immunostaining. The 3-NT staining was significantly increased in the hippocampi of the hyperoxic group. The normoxic group showed a 51.0% reduction of staining in the CA1 region compared with the hyperoxic group and a 50.8% reduction in the CA3 region (p < 0.05, both regions). There was no significant difference in staining between the injured normoxic group and sham-operated control groups. In the delayed analysis of neuronal survival (neuronal counts), there was no significant difference between the hyperoxic and normoxic groups. In this clinically relevant model of TBI, normoxic resuscitation significantly reduced oxidative damage to proteins compared with hyperoxic resuscitation. Neuronal counts showed no benefit from hyperoxic resuscitation. These findings indicate that hyperoxic ventilation in the early stages after severe TBI may exacerbate oxidative damage to proteins.