ABSTRACT
BACKGROUND: We have recently shown neuroprotective activity of the creatine amides in the focal cerebral ischemia in rats on the 280 mg/kg administration. In the present study, neuroprotective properties of creatylglycine ethyl ester fumarate (CrGEt) in rats with focal cerebral ischemia were explored in a wide dosage range (30-280 mg/kg, intravenous and intragastric). METHODS: Focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO). RESULTS: The CrGEt administration 30 minutes before and at the last 5 minutes of MCAO dose dependently attenuated cerebral ischemic damage on 35%-65%, reduced neurobehavioral deficits, led to high neuronal survival in ischemic rat brains. The neuroprotective activity of CrGEt was mediated by its following abilities: (1) normalize the energy metabolism in the ischemic brains, maintaining adenosine triphosphate levels, and reducing lactate concentration; (2) inhibit the ischemia-reperfusion-related oxidative stress as evidenced by the increased activity of superoxide dismutase and the reduced levels of malondialdehyde. CrGEt served as a substrate for creatine kinase and a partial agonist of N-methyl-D-aspartate receptors; this partly explains mechanism of its neuroprotective action. CONCLUSIONS: In view of the previously mentioned results, CrGEt holds a promise as a compound for treatment of ischemic brain disorders.
