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 phosphocreatine (PCr). Electrophysiological evidence suggests that this effect can protect neurons from anoxic damage by delaying the depletion of ATP during oxygen deprivation. In this paper we show that incubation of brain slices with varying doses of creatine increases intracellular phosphocreatine and delays anoxic depolarization (AD) in a dose-dependent way. Specifically, addition to the incubation medium of 1 mM creatine significantly increased AD latency during hypoxia and prevented irreversible neuronal damage. Adding 0.5 mM creatine had no significant effect. Higher concentrations of creatine (up to 25 mM) did not provide any better protection. Our data also suggest a linear correlation between intracellular PCr and AD latency. These data report neural protection by exogenous creatine at concentrations lower than those usually reported in the literature.
Balestrino
M
M
Department of Neurological Sciences, University of Genova, Via De Toni 5, 16132, Genoa, Italy.
Rebaudo
R
R
Lunardi
G
G
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003401:Creatine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000737:chemistry; D008564:Membrane Potentials / Q000187:drug effects; D010725:Phosphocreatine / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D010725:Phosphocreatine; D003401:Creatine