alpha-Phenyl-tert-N-butyl nitrone (PBN) improves functional and morphological outcome after cortical contusion injury in the rat

alpha -Phenyl-tert-N-butyl nitrone (BBN), a potent reactive oxygen species (ROS) scavenger, has shown robust neuroprotective properties in several mod els of acute brain injury, although not previously evaluated in traumatic b rain injury (TBI). In this study, we assessed the potential efficacy of PEN in a weight drop model producing a controlled cortical contusion. Sham ope ration, mild or severe injury was induced in intubated and ventilated rats and functional and morphological outcome was used as end-points at two week s postinjury. In the trauma groups, saline or PEN (30 mg/kg) was injected a s an intravenous bolus 30 minutes prior to injury. At day 11-15 post-injury , cognitive disturbance was assessed using the Morris Water Maze (MWM) and estimation of lesion volume and hemispheric loss of tissue was made. No cha nge in MWM performance were found in either of the mildly traumatized group s as compared to uninjured controls. In contrast, a significant decrease in total mean latency and increase in path length in the severely traumatized rats were found. PEN-treatment significantly improved MWM performance as c ompared to saline treatment at the severe injury level (p < 0.05). The mild injury level caused a discrete atrophy of the ipsilateral cortex with no e ffect of PEN treatment. The severe injury caused a substantial loss of ipsi lateral hemispheric tissue and a large cortical cavitation. PEN pre-treatme nt significantly reduced the lesion volume and reduced hemispheric loss of tissue at this injury level (p < 0.05). Our results support the involvement of ROS in the injury process contributi ng to the tissue loss and cognitive disturbance after TBI. The potential cl inical utility of PEN will have to be assessed using a post-injury dosing r egime.