Pretreatment with α-Phenyl-N-tert-butyl-nitrone (PBN) Improves Energy Metabolism after Spinal Cord Injury in Rats

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Abstract
We evaluated in rats, the effect of the spin trap alpha-phenyl-N-tert-butyl nitrone (PBN) on energy metabolism after severe spinal cord injury (SCI). A laminectomy of vertebrae Th7 and Th8 was made. A probe was inserted in a dorsal horn, and microdialysis was performed for 1.5 h before and 4 h after applying severe compression (4.5 g/mm2) for 5 min. Thirty minutes before trauma 30-mg/kg PBN or saline was given intravenously and a second dose of 10 mg/kg after 3 h. Microdialysis samples were collected at intervals of 10 min and analysed by high performance liquid chromatography. As reported previously there was a severalfold rise of lactate after trauma. The mean level of lactate was consistently lower in animals pretreated with PBN, but the difference was statistically significant between the groups only at 200 min after trauma. Lactate normalized more rapidly in PBN pretreated animals. In saline-treated rats, hypoxanthine quickly rose and reached a maximum 23 times above basal level 20 min after trauma, while the rise was 14 times in PBN pretreated rats. The increase of hypoxanthine was significantly lower and normalized more rapidly in PBN pretreated animals. This study suggests that PBN pretreatment attenuates lactic acidosis and improves energy metabolism after severe SCI. The effect may, at least partly, reflect amelioration of radical induced mitochondrial dysfunction.