Objective In the current study we investigated long-term behavioral outcome after cerebral hypoxia ischemia in neonatal rats as a basis to evaluate the long-term benefits of creatine supplementation. Previous findings showed that creatine supplementation preserves energy metabolism and thus ameliorates the extent of brain edema seen after transient cerebral hypoxia-ischamia.

Methods Creatine suppl. for 3 days was followed by right common carotid artery ligation and exposure to hypoxia of 8% O₂ for 60 min on day 7. 22 animals were creatine supplemented, 14 of them underwent hypoxic-ischemic intervention (Cr/HI). 11 animals underwent hypoxic-ischemic intervention without creatine suppl. (HI) and 10 animals were kept at the same condition without intervention (Con).

Results When compared with controls (Con) after 7–8 months, hypoxic-ischemic animals (HI) performed significantly worse in all behavioral tests: 0.56 (0.0–1.4, 25–75% percentile) versus 1.68 (1.4–2.5) sec searching time (p<0.001) in the platforme zone in the Morris water maze; 83 (70–126) versus 158 (128–206) sec running time on the rotarod (p = 0.029); 76.0 (24–218) versus 17.5 (6–80) asymmetric rotation after apomorphine injection (p = 0.013). Creatine suppl. and hypoxic-ischemic animals (Cr/HI) showed improvement compared with the hypoxic-ischemic animals (HI) in the morris water maze test and the rotarod without reaching statistical significance.

Conclusions This is the first study on this model showing long-term behavioral deficits after cerebral hypoxia-ischemia; this is an important condition for long-term evaluation of potential neuroprotective interventions. Small group size may account for non-significant improvement after creatine suppl. suggesting further investigation.