Exogenous creatine delays anoxic depolarization and protects from hypoxic damage: dose-effect relationship

Incubation of hippocampal slices with different concentrations of creatine (0.5, 1, 10, 25 mM) results in a dose-dependent increase in intracellular p hosphocreatine (PCr). Electrophysiological evidence suggests that this effe ct can protect neurons from anoxic damage by delaying the depletion of ATP during oxygen deprivation. In this paper we show that incubation of brain s lices with varying doses of creatine increases intracellular phosphocreatin e and delays anoxic depolarization (AD) in a dose-dependent way. Specifical ly, addition to the incubation medium of 1 mM creatine significantly increa sed AD latency during hypoxia and prevented irreversible neuronal damage. A dding 0.5 mM creatine had no significant effect. Higher concentrations of c reatine (up to 25 mM) did not provide any better protection. Our data also suggest a linear correlation between intracellular PCr and AD latency. Thes e data report neural protection by exogenous creatine at concentrations low er than those usually reported in the literature. (C) 1999 Elsevier Science B.V. All rights reserved.