Activity of ornithine decarboxylase and S-adenosylmethionine decarboxylase in transient cerebral ischemia: Relationship to the duration of vascular occulusion

Abstract

Mongolian gerbils were anesthetized with halothane and forebrain ischemia was induced by occluding both common carotid arteries. After 2, 4, 6, 8, or 10 min of vascular occlusion clips were removed and animals allowed to recover for 8 or 24 h. At the end of the experiments animals were reanesthetized and their brains frozen in situ. Tissue samples were taken from the cerebral cortex, striatum, hippocampus, and thalamus for determination of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) activity by measurement of the release of 14CO 2 from [ 14C]ornithine and S-[ 14C]adenosylmethionine, respectively. A transient increase in ODC activity was found after 8 h of recirculation following cerebral ischemia in all brain structures studied. ODC activity was significantly increased after 8 h of recirculation in the hippocampus of animals subjected to 4 min of ischemia, in the cortex and striatum after 6 min of ischemia, and in the thalamus after 8 min of vascular occlusion. ODC activity had already reached a plateau in the hippocampus after 4 min of vascular occlusion and in the cortex, striatum, and thalamus after 8 min, since there is no further increase in activity even after 10 min of ischemia. After cerebral ischemia and 24 h of recirculation ODC activity returned to control levels throughout the forebrain regardless of the duration of ischemia. SAMDC activity was significantly reduced after 8 h of recirculation following 4 to 10 min of ischemia in the cortex and 8 min of ischemia in the striatum. After 24 h of recirculation a significant reduction of SAMDC activity was measured in the cortex of animals subjected to 8 or 10 min of ischemia, in the striatum following 6 or 10 min of ischemia, and after 10 min of ischemia in the hippocampus. In control animals the SAMDC/ODC activity ratio (as an index of the extent of the disturbance of polyamine synthesis) ranged between 54.3 ± 17.2 (thalamus) and 172.4 ± 54.7 (cortex). After only 4 min of ischemia and 8 h of recirculation this ratio declined to 2.8 ± 1.7 in the vulnerable hippocampus but was still between 26.2 ± 18.4 (cortex) and 39.9 ± 50.5 (striatum). It is suggested that studying ischemia-induced changes in ODC and SAMDC activity may provide new information about the molecular mechanisms underlying stress-induced changes in gene experession and protein synthesis.