Anoxic ATP depletion in neonatal mice brainstem is prevented by creatine supplementation

Background-Sufficient ATP concentrations maintain physiological processes a nd protect tissue from hypoxic damage. With decreasing oxygen concentration , ATP synthesis relies increasingly on the presence of phosphocreatine. Aim-The effect of exogenously applied creatine on phosphocreatine and ATP c oncentrations was studied under control and anoxic conditions. Methods-Pregnant mice were fed orally with creatine monohydrate (2 g/kg bod y weight/day), Brainstem slices from these mice pups were compared with tho se from pups of non-creatine supplemented pregnant mice. Measurements were performed under normoxic and anoxic conditions, In addition, brainstem slic es from non-creatine treated mice pups were incubated for 3 hours in contro l artificial cerebrospinal fluid (CSF) (n = 10) or in artificial CSF contai ning 200 mu M creatine (n = 10). ATP and phosphocreatine contents were dete rmined enzymatically in single brainstem slices. Results-ATP concentrations were in the same range in all preparations. Howe ver, there was a significant increase of phosphocreatine in the brainstems from pups of creatine fed mice when compared with the brainstems of pups fr om non-creatine treated mice or in non-incubated brainstems of control anim als. After 30 minutes anoxia, ATP as well as phosphocreatine concentrations remained significantly higher in creatine pretreated slices compared with controls. Conclusion-The data indicate that exogenous application of creatine is effe ctive in neuroprotection.