Anoxic ATP depletion in neonatal mice brainstem is prevented by creatine supplementation.
BACKGROUND
Sufficient ATP concentrations maintain physiological processes and protect tissue from hypoxic damage. With decreasing oxygen concentration, ATP synthesis relies increasingly on the presence of phosphocreatine.


OBJECTIVE
The effect of exogenously applied creatine on phosphocreatine and ATP concentrations was studied under control and anoxic conditions.


METHODS
Pregnant mice were fed orally with creatine monohydrate (2 g/kg body weight/day). Brainstem slices from these mice pups were compared with those from pups of non-creatine supplemented pregnant mice. Measurements were performed under normoxic and anoxic conditions. In addition, brainstem slices from non-creatine treated mice pups were incubated for 3 hours in control artificial cerebrospinal fluid (CSF) (n = 10) or in artificial CSF containing 200 microM creatine (n = 10). ATP and phosphocreatine contents were determined enzymatically in single brainstem slices.


RESULTS
ATP concentrations were in the same range in all preparations. However, there was a significant increase of phosphocreatine in the brainstems from pups of creatine fed mice when compared with the brainstems of pups from non-creatine treated mice or in non-incubated brainstems of control animals. After 30 minutes anoxia, ATP as well as phosphocreatine concentrations remained significantly higher in creatine pretreated slices compared with controls.


CONCLUSIONS
The data indicate that exogenous application of creatine is effective in neuroprotection.
Wilken
B
B
Klinik für Pädiatrie und Neuropädiatrie, Universität Göttingen, 37075 Göttingen, Germany.
Ramirez
J M
JM
Probst
I
I
Richter
D W
DW
Hanefeld
F
F
D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000172:deficiency*; D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism; D003401:Creatine / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*; D010725:Phosphocreatine / Q000378:metabolism*; D011247:Pregnancy
D018696:Neuroprotective Agents; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003401:Creatine