Neuroprotective Effect of Pharmacological Preconditioning with Dicholine Succinate in Experimental Ischemic Stroke in Rats

Ischemic stroke is currently considered as one of the most pressing public health issues. Despite the differences in underlying mechanisms of ischemic and ischemic-reperfusion damage to the nervous tissue, the ultimate percentage of disability depends on intervention effects on the penumbra zone. The use of dicholine succinate (DCS), a neuronal insulin-sensitizer, is a promising pharmacological agent for management and prevention of stroke consequences.

The aim of the study was to investigate the effect of pharmacological preconditioning with DCS on brain cell death in experimental ischemic stroke in rats.

Materials and methods. Ischemic stroke in rats (N=16) was modeled by injecting the vasoconstrictor endothelin-1 (ET-1) into the striatum. The effect of pharmacological preconditioning with DCS as the active substance was evaluated by measuring the area of brain infarction in brain sections stained with cresyl violet. The effect of DCS on glycolysis and oxidative phosphorylation in primary cultures of rat cerebellum cells was assessed by measuring the rate of extracellular acidification and the rate of oxygen uptake, respectively.

Results. DCS administration in the preconditioning mode for 7 days, once a day orally, at a dose of 50 mg/kg, reduces the maximum area of the brain infarction zone by 34% (P<0.05) compared to the control in the subsequent experimental ischemic stroke induced by ET-1 administration. Three-day incubation of rat cerebellum primary culture with 50 µM DCHS does not affect the basal levels of glycolysis (P=0.916) and cellular respiration (P=0.8346), but increases cellular glycolytic reserve by 70.0% (P<0.0001) compared to the control.

Conclusion. For the first time, the neuroprotective effect of pharmacological preconditioning with the neuronal insulin-sensitizer DCS in ischemic stroke has been shown. Mechanism of DCS action associates with an increase in the glycolytic reserve of brain cells, i.e., with increased ability of preconditioned cells to produce ATP and lactate via glycolysis in case of acutely compromised oxidative phosphorylation.

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