Gibson_1988_Neurochem.Res_13_9

An in vitro model of anoxic-induced brain damage was developed to help elucidate the biochemical basis of cell damage due to reduced oxygen availability. Mouse forebrain slices were preincubated under various conditions (treatment incubation). The effects of this treatment incubation on [14C]acetylcholine (ACh) and 14CO2 production from [U-14C]glucose were subsequently assessed in an incubation under optimal conditions (test incubation). A variety of treatment incubation conditions decreased 14CO2 and 14C-ACh production in the test incubation in parallel (r = 0.932). For example, treatment incubations with no oxygen and high K+ reduced test incubation ACh (-63.2%) and CO2 (-67.3%) production. An anoxic-induced increase in calcium-45 uptake and the amelioration of anoxic induced changes by the calcium antagonist verapamil or by the omission of calcium from the treatment incubation suggest that altered calcium homeostasis was important in the production of the anoxic-induced deficits. These results provide in vitro evidence that anoxic induced increases in calcium may be pathophysiologically important and that reducing calcium entry postsynaptically may alleviate anoxic-induced changes. This model may prove useful in elucidating the molecular basis of these changes.