The neuroprotective effect of ischemic postconditioning and citicoline against cerebral ischemia-reperfusion injury in mongolian gerbils

Abstract

Background. Ischemic postconditioning (IPostC) - a phenomenon of cerebral infarct volume reduction after a series of short ischemic stimuli in the early reperfusion period after prolonged ischemia. The mechanisms of IPostC remain poorly studied; in addition, the effects of combined application of pharmacological neuroprotection and IPostC are not investigated that precludes the translation of IPostC to the clinical practice. Objective. To assess the neuroprotective effect of IPostC and neuroprotective agent citicoline, and the effect of their combined application in the experimental model of global cerebral ischemia-reperfusion. Materials and methods. Transient global cerebral ischemia was induced by bilateral occlusion of the common carotid arteries in Mongolian gerbils for 7 minutes. IPostC was induced by three 15-s episodes of reperfusion/reocclusion. Citicoline was administered intraperitoneally at a dose of 500 mg/kg 2 min after the start of ischemia. In a separate series of experiments, the combined application of IPostC and citicoline was used. The number of viable neurons in the CA1 hippocampus was used as an and-point of neuroprotection. Results. In the experimental groups using IPostC, citicoline administration at a dose of 500 mg/kg, as well as their combined use a significant (p < 0,05) increase in the number of viable pyramidal neurons in the CA1 hippocampus was observed when compared with control group. The combined use of citicoline and IPostC did not provide an additional increase in the number of viable neurons. Conclusions. The combined use of citicoline and IPostC resulted in the expression of a significant neuroprotective phenotype, but its magnitude was not different from that in the groups of isolated citicoline and IPostC use.