ALTERATIONS IN THE PRODUCTION OF CO2-C-14 AND [C-14] ACETYLCHOLINE FROM [U-C-14]GLUCOSE IN BRAIN SUBREGIONS FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA IN THE RAT

Abstract: The production of 14CO2 and [14C]acetylcholine from [U‐14C]glucose was determined in vitro using tissue prisms prepared from the dorsolateral striatum (a region developing extensive neuronal loss following ischemia) and the paramedian neocortex (an ischemia‐resistant region) following 30 min of forebrain ischemia and recirculation up to 24 h. Measurements were determined under basal conditions (5 mMK+) and following K+ depolarization (31 mM K+). The production of 14CO2 by the dorsolateral striatum was significantly reduced following 30 min of ischemia for measurements in either 5 or 31 mM K+ but recovered toward preischemic control values during the first hour of recirculation. Further recirculation resulted in 14CO2 production again being reduced relative to control values but with larger differences (20–27% reductions) detectable under depolarized conditions at recirculation times up to 6 h. Samples from the paramedian neocortex showed no significant changes from control values at all time points examined. [14C]Acetylcholine synthesis, a marker of cholinergic terminals that is sensitive to changes in glucose metabolism in these structures, was again significantly reduced only in the dorsolateral striatum. However, even in this tissue, only small (nonstatistically significant) differences were seen during the first 6 h of recirculation, a finding suggesting that changes in glucose oxidation during this period were not uniform within all tissue components. The results of this study provide evidence that in a region susceptible to ischemic damage there were specific changes during early recirculation in the metabolic response to depolarization. This apparent inability to respond appropriately to an increased need for energy production could contribute to the further deterioration of cell function in vivo and ultimately to the death of some cells. Copyright © 1990, Wiley Blackwell. All rights reserved