A pharmacological model of ischemia in the hippocampal slice

The effects of various metabolic inhibitors on the time course of changes in membrane potential was studied using intracellular recordings from CA1 hippocampal neurons in vitro. Concurrent application of cyanide and iodoacetic acid, agents which block oxidative phosphorylation and glycolysis respectively, result in more rapid loss of membrane function than blockade of either pathway alone. This pharmacological regimen mimics the anoxia and the hypoglycemia encountered during ischemia in vivo, both in terms of the metabolic derangement as well as the time course of changes in membrane function. Thus, this treatment appears to represent a well-controlled pharmacological model of ischemia in vitro.