Neuroprotective Effect of Lithium Chloride in Rat Model of Cardiac Arrest

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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