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 insu lt. The preconditioning mechanism induced by adenosine ("the adenosine mech anism") was characterized in primary rat neuronal cultures, employing a mod el of chemical ischemia. The protective mechanism, initiated by activation of adenosine receptors, consists of a signal transduction pathway, involvin g activation of protein kinase C (PKC) and opening of ATP-sensitive potassi um (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-AT P channels mediates the signal activated by the adenosine receptors, and pr obably also that activated by PKC. The acquired ischemic resistance lasts u p to 5 days, depending on the activating substance. The adenosine-activated cascade of events leading to ischemic tolerance in neurons is similar to t hat operating in cardiomyocytes. (C) 2000 Elsevier Science Inc. All rights reserved.