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 microns resolution. Each 75 x 75 microns 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Subclinical Compromise in Cardiac Strain Relates to Lower Cognitive Performances in Older Adults

“…First, subclinical reductions in CBF can result in oligemia or mild reductions in regional CBF. Oligemia can affect protein synthesis required for synaptic plasticity associated with learning and memory 35, 36. In addition, the temporal lobes appear especially vulnerable to CBF reductions possibly due to a less extensive network of collateral blood flow sources 37.…”

The CBF Threshold and Dynamics for Focal Cerebral Infarction in Spontaneously Hypertensive Rats

“…Pollowing permanent common carotid artery occlusion and transient (30 min) hy potension, pathological changes 2.5 h after ischemia onset were correlated to CBP values averaging slightly less than 50 mll00 g-I min -I (measured 15 min after ischemia onset) in the deepest layers of the cortex (Mendelow et al, 1984). Moreover, CBP values in the 40-50 ml 100 g -I min -I range (mea sured 2-2.5 h after the onset of focal ischemia) pro voke major changes in protein synthesis (Mies et al, 1991) the expression of heat shock proteins (Jacewicz et al, 1986), and cerebral acidosis (Nakai et aI., 1988;Kaplan et aI., unpublished observa tions). Although these seemingly high blood flows appear to be noxious, it remains to be proven that such flows (a) irreversibly injure brain cells and (b) are not preceded or followed by lower CBF levels that could trigger injury.…”

Inhibition of Nonselective Cation Channels Reduces Focal Ischemic Injury of Rat Brain

“…The other major protective mechanism of LOE 908 MS seems to be the preservation of energy metabolites under conditions of critically reduced blood flow. In pre vious studies from our laboratory (Mies et a!., 1991;Kohno et aI., 1995), evidence has been provided that the CBP threshold for ATP depletion steadily increases from 13 ml 100 g-l min-1 after 30-min ischemia to 19 ml 100 g-1 min-1 after 1 h and to 23 ml 100 g-1 min-1 after 6 h. The present CBP threshold of 20 ml 100 g-I min-I for the untreated group at 6 h of MCA occlusion comes close to the expected value after this duration of ischemia. CBP threshold for the treated group, in contrast, re mained stable at 15 ml 100 g-1 min-I , which corresponds with the prevention of infarct core expansion.…”