Общая реаниматология (Jul 2019)
Neuroprotective Effect of Lithium Chloride in Rat Model of Cardiac Arrest
Abstract
Lithium chloride, which is used for the treatment of bipolar disorders, has a neuroprotective effect in conditions associated with acute and chronic circulatory disorders.The purpose of the study: to investigate the efficacy of lithium chloride for the prevention of post-resuscitation death of hippocampal neurons during the post-resuscitation period.Material and methods. Cardiac arrest for 10 minutes was evoked in mature male rats by intrathoracic clumping of the vascular bundle of the heart, followed by resuscitation. 40 mg/kg or 20 mg/kg of 4,2% lithium chloride (LiCl) was injected intraperitoneally 1 hour before cardiac arrest, on the 1st and 2nd day after resuscitation (n=9). Untreated animals received equivalent doses of saline (n=9). Rats after a sham surgery served as a reference group (n=10). The number of viable neurons in the CA1 and CA3/CA4 fields of the hippocampus was estimated in slides stained with cresyl violet by day 6 or 7 postresuscitation. In a separate series of experiments, at the same terms, we studied the effect of lithium chloride on the protein content of GSK3β (glycogen synthase kinase) in brain tissue using Western-Blot analysis.Results. Histological assay showed that a 10-minute cardiac arrest resulted in a decrease in the number of viable neurons in the hippocampal CA1 field — by 37.5% (P0.001), in the CA3/CA4 field — by 12.9% (P0.05) vs. the reference group. Lithium treatment increased the number of viable neurons in resuscitated rats — in the CA1 field by 37% (P<0.01), in the CA3/CA4 field — by 11.5% (P0.1) vs. the untreated animals. It was found that lithium caused an increase in phosphorylated form of GSK3β: by 180% vs. the reference group (P[1]0.05), and by 150% vs. the untreated animals (P0.05).Conclusion. Lithium treatment leads to a pronounced neuroprotection in the neuronal populations of the hippocampus post-resuscitation. This effect may be due to an increase in the content of the phosphorylated form of GSK3β protein. The results indicate a high potential of lithium for the prevention and treatment of neurodegenerative disorders caused by a temporary arrest of blood circulation.
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