MICROGLIAL RESPONSES AFTER FOCAL RADIATION-INDUCED-INJURY ARE AFFECTED BY ALPHA-DIFLUOROMETHYLORNITHINE

Purpose: The objective of this study was to quantify microglial and as trocytic cell responses after focal I-125 irradiation of normal brain and to determine the effects of an intravenous infusion of alpha-diflu oromethylornitbine (DFMO) on those responses. Methods and Materials: A dult beagle dogs were irradiated using high activity I-125 sources, Sa line or DFMO (75 mg/kg/day) was infused for 18 days, and 1 to 10 weeks later brain tissues were collected. Immunohistochemical stains were u sed to label phagocytes and amoeboid microglia (lectin RCA-1), astrocy tes (GFAP), and cells synthesizing deoxyribonucleic acid (DNA) (BrdU). Cell densities (cells/mm(2)) and BrdU labeling indices were quantifie d. Results: In dogs infused with saline, increases in phagocytes and a moeboid microglia were observed at 1-2 weeks and 4 weeks, respectively . The labeling indices for phagocytes and amoeboid microglia peaked at 4 weeks with maximum values of 4.8 and 13.4%, respectively. Astrocyte cell numbers increased from 2-6 weeks following irradiation; increase d labeling indices were observed after 2 weeks. An infusion of DFMO si gnificantly suppressed BrdU labeling and delayed the increase in cell numbers for phagocytes and amoeboid microglia. In both treatment group s, the proportion of total BrdU labeling accounted for by phagocytes w as maximum 1 week after irradiation and then decreased. The proportion of total BrdU labeling accounted for by amoeboid microglia and astroc ytes was zero for 2 weeks and then increased. Conclusions: Microglial reactions after focal irradiation involve the phagocytic and amoeboid cell forms and are characterized by increased BrdU uptake and increase d cell number. DFMO significantly alters these responses. Changes in a strocyte cell number and BrdU labeling may be related to changes in mi croglia, Studies of cell responses and their modification may lead to a better understanding of the pathogenesis of radiation injury, and to new strategies to optimize the use of therapeutic irradiation.