Experimental substantiation of the expediency of the combined use of piracetam and metformin for pharmacological correction of cognitive disorders in conditions of prolonged hyperglycemia

Chronic hyperglycemia, insulin resistance, endothelial dysfunction, and disturbance of the integrity of the blood-brain barrier are considered as strategically important links in the development of cognitive deficits in diabetic encephalopathy. Taking this into account, one of the modern trends in the optimization of the treatment of cognitive impairments induced by prolonged hyperglycemia is the co-administration of agents with antihyperglycemic and nootropic activity, in particular, metformin with piracetam. It has been shown that under conditions of experimental alloxan-induced hyperglycemia, piracetam has insufficient nootropic potential for eliminating cognitive deficits. Metformin has a weak nootropic effect in short-term use in low doses, without exhibiting these properties in prolonged administration. When combined with piracetam, metformin potentiates its antiamnesic properties, which helps to restore cognitive functions impaired by hyperglycemia. It is assumed that the mechanisms of such synergism are mediated by a decrease in the content of early and late markers of the destruction of protein molecules, the level of stable nitric oxide metabolites in the cerebral cortex, as well as a significant limitation of the manifestations of ultrastructural destructive changes in hippocampal neurons with a simultaneous improvement in the state of its microvasculature. The obtained results indicate the expediency of the combined use of metformin with nootropic agents for the prevention or treatment of cognitive impairments that occur as a result of diabetes mellitus.