DIFLUOROMETHYLORNITHINE DECREASES POSTISCHEMIC BRAIN EDEMA AND BLOOD-BRAIN-BARRIER BREAKDOWN

BRAIN POLYAMINES HAVE been associated with posttraumatic vasogenic ede ma and blood-brain barrier (BBB) breakdown seen in some models of brai n injury. We hypothesized that the inhibition of the enzyme responsibl e for polyamine production with the decarboxylase difluoromethylornith ine (DFMO) may decrease BBB breakdown after a focal brain ischemic str oke. Thirty-two cats underwent 8 hours of middle cerebral artery occlu sion and one of four treatments: sham operation (Sham), ischemia (Isc) , ischemia/DFMO (Isc/DF), and ischemia/DFMO/putrescine (Isc/DF/PU). Th e regional brain specific gravity and the volume of Evans blue (EB) ex travasation were measured at the time of death. The groups were monito red for temperature, heart rate, blood pressure, and arterial blood ga ses, and the values did not differ outside normal physiological ranges . EB results were expressed as the percentage of the hemisphere staine d and showed the following: Sham, 2.23%; Isc, 32.8%; Isc/DF, 5.6%; Isc /DF/PU, 36.3%. As a measure of BBB, ischemia increased EB staining; DF MO pretreatment decreased the amount of EB staining to control levels; and the polyamine putrescine abolished the protective effect of DFMO (all significant at P = 0.05). DFMO pretreatment also resulted in a si gnificant (P = 0.05) return to control values for specific gravity in the EB-stained regions (1.0328) of ischemic animals' This effect was p resent primarily in the white matter. Treatment with DFMO, an ornithin e decarboxylase inhibitor, significantly decreased postischemic BBB br eakdown and vasogenic edema in this model.