Contribution of polyamine oxidase to brain injury after trauma.
OBJECTIVE
The possible role of the polyamine interconversion pathway on edema formation, traumatic injury volume, and tissue polyamine levels after traumatic brain injury (TBI) was studied using an inhibitor of the interconversion pathway enzyme, polyamine oxidase.


METHODS
Experimental TBI was induced in Sprague-Dawley rats by using a controlled 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 N1,N4-bis(2,3-butadienyl)-1,4-butanediamine 2HCl (MDL 72527) or saline was injected intraperitoneally. Brain water content and tissue polyamine levels were measured 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 mm3 compared with 42.7+/-13.3 mm3, p < 0.05) compared with the saline treatment. The TBI caused a significant increase in tissue putrescine levels at the traumatized site (65.5+/-26.5 nmol/g [corrected] in the cortex and 70.9+/-22.4 nmol/g [corrected] in the hippocampus) compared with the nontraumatized site (7+/-2.4 nmol/g [corrected] in the cortex and 11.4+/-6.4 nmol/g [corrected] in the hippocampus). The increase in putrescine levels in both the traumatized and nontraumatized cortex and hippocampus was reduced by a mean of 60% with MDL 72527 treatment.


CONCLUSIONS
These results demonstrate, for the first time, that the polyamine interconversion pathway has an important role in the increase of putrescine levels after TBI and that the polyamine oxidase inhibitors, blockers of the interconversion pathway, can be neuroprotective against edema formation and necrotic cavitation after TBI.
Doğan
A
A
Department of Neurological Surgery, University of Wisconsin and Veterans Administration Hospital, Madison 53792, USA.
Rao
A M
AM
Baskaya
M K
MK
Hatcher
J
J
Temiz
C
C
Rao
V L
VL
Dempsey
R J
RJ
D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors / Q000502:physiology*; D011073:Polyamines / Q000378:metabolism; D011700:Putrescine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097667:Polyamine Oxidase
D004791:Enzyme Inhibitors; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D011700:Putrescine; D000097667:Polyamine Oxidase; C044445:MDL 72527