The adenosine-induced mechanism for the acquisition of ischemic tolerance in primary rat neuronal cultures

Neurons can be preconditioned by various procedures to resist ischemic insult. The preconditioning mechanism induced by adenosine ("the adenosine mechanism") was characterized in primary rat neuronal cultures, employing a model of chemical ischemia. The protective mechanism, initiated by activation of adenosine receptors, consists of a signal transduction pathway, involving activation of protein kinase C (PKC) and opening of ATP-sensitive potassium (K-ATP) channels. Direct activation (and inhibition) of PKC, as well as opening of K-ATP channels, also confers protection. The opening of the K-ATP channels mediates the signal activated by the adenosine receptors, and probably also that activated by PKC. The acquired ischemic resistance lasts up to 5 days, depending on the activating substance. The adenosine-activated cascade of events leading to ischemic tolerance in neurons is similar to that operating in cardiomyocytes. (C) 2000 Elsevier Science Inc. All rights reserved.