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Oxidative stress is an important pathogenetic factor in cerebral ischemia, which occupies one of the leading places among various forms of cerebral pathology in mortality and disability of the working-age population and is recognized as an actual problem of experimental and clinical neurology. One way to reduce damage and mortality from strokes is to study the mechanisms of ischemia by modeling its damaging factors and in vitro protection methods. To reveal the influence of chemical preconditioning induced by transient inhibition of Na+/K+-ATPase activity on tolerance of cultured cerebellar granule neurons to oxidative stress at different stages of their differentiation in vitro. The activity of Na+/K+-ATPase was inhibited with ouabain, which was added at 3–4 and 7–8 days in vitro to cerebellar cell cultures of 7-day rats at a concentration of 0.1 mM for 24 hours before induction of oxidative stress by hydrogen peroxide (0.05 and 0.075 mM, 4 hours) or paraquat (0.15 and 0.2 mM, 24 hours). Oxidative stress induced by paraquat caused the most pronounced death of cultured granule neurons in immature (3–4 days) cultures, in which survival was 44 ± 2.5% of neurons, compared to mature (7–8 days) cultures, in which survival was 61 ± 5.4%. Pretreatment of cultures with ouabain had a protective effect, the most significant in mature cultures. The exposure of mature cultures to hydrogen peroxide killed more than 90% of neurons, whereas pretreatment with ouabain increases the viability by 44%. At the same time, in immature cultures the damaging effect of Н2О2 and the protective effect of ouabain were less pronounced. The increased tolerance of cultured cerebellar granule cells to oxidative stress after transient inhibition of Na+/K+-ATPase activity by ouabain is shown. The direct dependence of the efficiency of the ouabain protection on the degree of neuronal morphochemical differentiation in vitro is revealed. [ABSTRACT FROM AUTHOR]