Effects of the nitrone radical scavengers PBN and S-PBN on in vivo trapping of reactive oxygen species after traumatic brain injury in rats

In previous studies, the authors showed that the nitrone radical scavenger alpha -phenyl-N-tert-butyl nitrone (PBN) and its sulfo-derivative, 2-sulfo- phenyl-N-tert-butyl nitrone (S-PBN), attenuated cognitive disturbance and r educed tissue damage after traumatic brain injury (TBI) in rats. In the cur rent study, the production of reactive oxygen species (ROS) after TBI was m onitored with microdialysis and the 4-hydroxybenzoic acid (4-HBA) trapping method. A single dose of PBN (30 mg/kg) or an equimolar dose of S-PBN (47 m g/kg) was administered intravenously 30 minutes before a controlled cortica l contusion injury in rats. Plasma and brain tissue drug concentrations wer e analyzed at the end of the microdialysis experiment (3 hours after injury ) and, in a separate experiment with S-PBN, at 30 and 60 minutes after inju ry. Traumatic brain injury caused a significant increase in ROS formation t hat lasted for 60 minutes after the injury as evidenced by increased 3,4-di hydroxybenzoic acid (3,4-DHBA) concentrations in the dialysate. PBN and S-P BN equally and significantly attenuated the posttraumatic increase in 3,4-D HBA formation. High PBN concentrations were found bilaterally in brain tiss ue up to 3 hours after injury. In contrast, S-PBN was rapidly cleared from the circulation and was not detectable in brain at 30 minutes after injury or at any later time point. The results suggest that scavenging of ROS afte r TBI may contribute to the neuroprotective properties observed with nitron e spin-trapping agents. S-PBN, which remained undetectable even in traumati zed brain tissue, reduced ROS production to the same extent as PBN that rea dily crossed the blood-brain barrier. This finding supports an important ro le for ROS production at the blood-endothelial interface in TBI.