[Cerebroprotective activity of metformin, gosogliptin, citicoline and a novel GPR119 agonist in cerebral ischemia under experimental diabetes mellitus]. / Sravnitel'naia tserebroprotektivnaia aktivnost' metformina, gosogliptina, tsitikolina i novogo agonista GPR119 pri éksperimental'noi ishemii golovnogo mozga na fone sakharnogo diabeta.

ABSTRACT

Hypoglycemic agents of some groups sodium-glucose cotransporter type 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists reduce the risk and/or severity of cardiovascular diseases. Studies of such properties are currently focused on metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors. Agonists of GPR119 receptor, increasing the secretion of GLP-1 and insulin, are also actively studied as hypoglycemic drugs with endothelial and cerebroprotective potential. AIM: To evaluate the cerebroprotective activity of metformin, gosogliptin, citicoline and an agonist of GPR119 (ZB-16) in middle cerebral artery occlusion (MCAO) in animals with 4-week streptozotocin-nicotinamide-induced diabetes. MATERIAL AND METHODS: A study included 73 male rats. Hypoglycemic agents and ZB-16 were administered on the first day of diabetes and citicoline was administered after MCAO. Cerebroprotective effect was evaluated using Garcia, Combs and D'Alecy score test, 'Rotarod' and 'open field' test, as well as the infarct volume and severity of brain edema measurement. RESULTS AND CONCLUSION: Preventive administration of metformin resulted in the pronounced hypoglycemic activity without a significant cerebroprotective effect in subsequent brain ischemia modelling. Administration of substances with incretin activity (gosogliptin and, in particular, ZB-16) in addition to the hypoglycemic action promoted a significant reduction of infarct volume, brain edema and severity of neurologic deficit of the surviving animals. At the same time, the introduction of citicoline without proper glycemic control didn't reduce the brain ischemia severity.