The Nitrone Free Radical Scavenger NXY-059 Is Neuroprotective when Administered after Traumatic Brain Injury in the Rat

摘要

Reactive oxygen species (ROS) are important contributors to the secondary injury cascade following traumaticnbrain injury (TBI), and ROS inhibition has consistently been shown to be neuroprotective following experimentalnTBI. NXY-059, a nitrone free radical trapping compound, has been shown to be neuroprotective in models ofnischemic stroke but has not been evaluated in experimental TBI. In the present study, a continuous 24-h intravenousninfusion of NXY-059 or vehicle was initiated 30 min following a severe lateral fluid percussion brainninjury (FPI) in adult rats (n紏22), and histological and behavioral outcomes were evaluated. Sham-injurednanimals (n紏22) receiving identical drug infusion were used as controls. Visuospatial learning was evaluated innthe Morris water maze at post-injury days 11–14, followed by a probe trial (memory test) at day 18. The animalsnwere sacrificed at day 18, and loss of hemispheric brain tissue was measured in microtubule-associated proteinn(MAP)–2 stained sections. Brain-injured, NXY-059-treated animals showed a significant reduction of visuospatialnlearning deficits when compared to the brain-injured, vehicle-treated control animals ( p < 0.05). NXY-059-treatednanimals significantly reduced the loss of hemispheric tissue compared to brain-injured controls (43.0u000211mm3nversus 74.4u000219mm3, respectively; p < 0.01). The results show that post-injury treatment with NXY-059 significantlynattenuated the loss of injured brain tissue and improved cognitive outcome, suggesting a major role fornROS in the pathophysiology of TBI.