ANOXIC PRECONDITIONING IN HIPPOCAMPAL SLICES - ROLE OF ADENOSINE

Prior studies have shown that sublethal anoxic/ischemic insults may '' precondition'' and thereby protect tissues such as heart and brain fro m subsequent insults. In hippocampal slices, we examined two hypothese s: (i) that anoxic preconditioning improves the ability of slices to r ecover synaptic activity following a second anoxic insult and (ii) tha t anoxic preconditioning involves adenosine receptors. Hippocampal sli ces were preconditioned by short periods of anoxia prolonged only unti l the onset of anoxic depolarization. The slices were then reoxygenate d for 30 min, after which a second (''test'') anoxic insult was induce d. Amplitudes of evoked potentials recovered significantly better afte r ''test'' anoxic insults in preconditioned slices. In control slices, transient superfusion with adenosine or an adenosine A1 receptor agon ist (2-chloroadenosine) 30 min prior to ''test'' anoxia markedly impro ved evoked potential recovery. Administration of 8-cyclopentyl-1,3-dip ropylxanthine, an A1 receptor antagonist, blocked the protection affor ded by preconditioning. These data support the hypothesis that adenosi ne, probably by its activation of A1 receptors, is involved in the neu roprotection afforded by anoxic preconditioning in hippocampal slices. Preconditioning insults may have a significant clinical impact, since certain surgical procedures may require, or produce, multiple periods of brain ischemia. Copyright (C) 1996 IBRO.