Contribution of polyamine oxidase to brain injury after trauma

Object. The possible role of the polyamine interconversion pathway on edema . formation, traumatic injury volume, and tissue polyamine levels after tra umatic brain injury (TBI) was studied using an inhibitor of the interconver sion pathway enzyme, polyamine oxidase. Methods. Experimental TBI was induced in Sprague-Dawley mts by using a cont rolled cortical impact device at a velocity of 3 m/second, resulting in a 2 -mm deformation. Immediately after TBI was induced, 100 mg/kg of N',N'-bis( 2,3-butadienyl)-1,-4-butanediamine 2HCl (MDL 72527) or saline was injected intraperitoneally. Brain water content and tissue polyamine levels were mea sured at 24 hours after TBI. Traumatic injury volume was evaluated using 2% cresyl violet solution 7 days after TBI occurred. The MDL 72527 treatment significantly reduced brain edema (80.4 +/- 0.8% compared with 81.2 +/- 1.2 %, p < 0.05) and injury volume(30.1 +/- 6.6 mm(3) compared with 42.7 +/- 13 .3 mm(3), p < 0.05 compared with the saline treatment. The TBI caused a sig nificant increase in tissue putrescine levels at the traumatized site (65.5 +/- 26.5 pmol/g in the cortex and 70.9 +/- 22.4 pmol/g in the hippocampus) compared with the nontraumatized site (7 +/- 2.4 pmol/g in the cortex and 11.4 +/- 6.4 pmol/g in the hippocampus). The increase in putrescine levels in both the traumatized and nontraumatized cortex and hippocampus was reduc ed by a mean of 60% with MDL 72527 treatment. Conclusions. These results demonstrate, for the first time, that the polyam ine interconversion pathway has an important role in the increase of putres cine levels after TBI and that the polyamine oxidase inhibitors, blockers o f the interconversion pathway, can be neuroprotective against edema formati on and necrotic cavitation after TBI.