ALTERATIONS IN [H-3]L-N-G-NITROARGININE BINDING IN BRAIN AFTER TRANSIENT GLOBAL OR TRANSIENT FOCAL ISCHEMIA IN GERBILS AND RATS

We investigated the post-ischemic change in [H-3]L-N-G-nitroarginine b inding as a marker of nitric oxide (NO) synthase in the animal brain a fter transient global ischemia or transient focal ischemia. Transient global ischemia in gerbils was induced for 10 min followed by 1 h to 7 days of recirculation. Transient focal ischemia in rats was induced f or 45 min followed by 3 days of recirculation. Following transient glo bal ischemia, [H-3]L-N-G-nitroarginine binding showed a significant in crease in the striatum (17-18%) and hippocampal CA1 sector (24%) at 48 and 24 h after recirculation, respectively. The hippocampal CA3 secto r also showed a significant elevation (32-40%) in [H-3]L-N-G-nitroargi nine binding at 24 and 48 h after global ischemia. Furthermore, the de ntate gyrus showed a significant increase (30-32%) in [H-3]L-N-G-nitro arginine binding at 5, 24 and 48 h after global ischemia. Thereafter, a significant reduction in [H-3]L-N-G-nitroarginine binding was observ ed only in the dentate gyrus 7 days after recirculation. In contrast, [H-3]L-N-G-nitroarginine binding was unchanged in the thalamus through out the recirculation periods. Histological analysis revealed that tra nsient global ischemia caused severe damage or cellular damage in the striatum and the hippocampal CA1 sector. The hippocampal CA3 sector an d thalamus were mildly damaged, whereas the dentate gyrus was morpholo gically intact. Following transient focal ischemia, a marked elevation (50-52%) in [H-3]L-N-G-nitroarginine binding was found in the regions of the ipsilateral striatum in which severe infarction occurred. Our findings suggest that [H-3]L-N-G-nitroarginine binding increases in th e striatum and hippocampus after transient global ischemia or transien t focal ischemia. This increase in [H-3]L-N-G-nitroarginine binding ma y play a pivotal role not only in the pathogenesis of ischemic brain d amage, but also in the restoration of injury areas after cerebral isch emia. (C) 1998 Elsevier Science B.V. All rights reserved.