Modification of radiation-induced brain injury by alpha-difluoromethylornithine.
The effect of alpha-difluoromethylornithine (DFMO) on 125I-induced brain injury was investigated in a dog model. Cerebrospinal putrescine levels were reduced from baseline levels 1-2 weeks after irradiation in animals treated with 125I and DFMO, while putrescine levels were elevated in 125I and saline-treated animals. In addition, the time course of changes in the volumes of edema, necrosis, and tissue showing evidence of blood-brain barrier breakdown was altered significantly by DFMO treatment. The most significant alterations occurred 2-4 weeks after irradiation, at which times the average volumes of damage in DFMO-treated animals were reduced compared to saline-treated animals. The time course of alterations in blood-to-brain transfer, brain-to-blood transfer, and vascularity following irradiation was also altered by DFMO treatment. Analysis of variance demonstrated a strong relationship of blood-to-brain transfer and vascularity to volume of edema, suggesting that the effect of DFMO on edema may be partially mediated by its effects on blood-brain barrier breakdown.
Gobbel
G T
GT
Department of Neurological Surgery, University of California, San Francisco 94143.
Marton
L J
LJ
Lamborn
K
K
Seilhan
T M
TM
Fike
J R
JR
D000818:Animals; D001812:Blood-Brain Barrier / Q000528:radiation effects; D001918:Brachytherapy; D001921:Brain / Q000473:pathology / Q000528:radiation effects*; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004285:Dogs; D000518:Eflornithine / Q000008:administration & dosage*; D005260:Female; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes / Q000008:administration & dosage; D008297:Male; D011700:Putrescine / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013095:Spermidine / Q000378:metabolism
D007457:Iodine Radioisotopes; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine