The amelioration of energy metabolic disturbance in
cerebral anoxia is valuable for the treatment of various cerebral ischemic diseases and insufficiency. In this study, the effect of
Y-8894 on the cerebral energy metabolism was investigated using a KCN-induced
cerebral anoxia model with mice. The
intravenous injection of a lethal dose of KCN (2.5 mg/kg) induced rapid and marked decreases of brain
glucose,
phosphocreatine and
ATP contents, with a remarkable enhancement of
lactate and
AMP levels, indicating a severe disorder of the cerebral energy metabolism. This phenomenon was also shown by an irreversible deterioration of the energy charge potential (ECP), an index of the cerebral energy state. The treatment with
Y-8894 (30 mg/kg, i.p.) remarkably ameliorated this KCN-induced energy metabolic disturbance: markedly reducing the changes in brain
phosphocreatine,
glucose and
lactate contents, while keeping
ATP,
AMP and ECP at nearly their normal levels. In addition, these changes in the
Y-8894 treated group recovered promptly to normal, whereas those in the control group were irreversible. In normal mice,
Y-8894 induced a significant increase in the cerebral
glucose content without affecting either the cerebral glycolytic metabolism or the energy state. The present findings suggest that
Y-8894 has an ameliorative effect on the cerebral energy metabolic disturbance, and this effect likely plays an important role in the improvement of
amnesia and other neurological deficits related to
cerebral anoxia.