Ischemic thresholds of cerebral protein synthesis and energy state following middle cerebral artery occlusion in rat

Abstract

The ischemic threshold of protein synthesis and energy state was determined 1, 6, and 12 h after middle cerebral artery (MCA) occlusion in rats. Local blood flow and amino acid incorporation were measured by double tracer autoradiography, and local ATP content by substrate-induced bioluminescence. The various images were evaluated at the striatal level in cerebral cortex by scanning with a microdensitometer with 75 μm resolution. Each 75 × 75 μm digitized image pixel was then converted into the appropriate units of either protein synthesis. ATP content, or blood flow. The ischemic threshold was defined as the flow rate at which 50% of pixels exhibited complete metabolic suppression. One hour after MCA occlusion, the threshold of protein synthesis was 55.3 ± 12.0 ml 100 g-1 min-1 and that of energy failure was 18.5 ± 9.8 ml 100 g-1 min-1. After 6 and 12 h of MCA occlusion, the threshold of protein synthesis did not change (52.0 ± 9.6 and 56.0 ± 6.5 ml 100 g-1 min-1. respectively) but the threshold of energy failure increased significantly at 12 h following MCA occlusion to 31.9 ± 9.7 ml 100 g-1 min-1 (p < 0.05 compared to 1 h ATP threshold value: all values are mean ± SD). In focal cerebral ischemia, therefore, the threshold of energy failure gradually approached that of protein synthesis. Our results suggest that with increasing duration of ischemia, survival of brain tissue is determined by the high threshold of persisting inhibition of protein synthesis and not by the much lower one of acute energy failure. If the ischemic penumbra is considered to comprise the region in which cerebral protein synthesis is suppressed and energy state is preserved, it follows that the size of the penumbra decreases with the duration of ischemia.