Protective effect of citicoline in acute reversible cerebral ischemia in rats

Abstract

Resume. Revascularization intervention for ischemic stroke has significant time and technological limitations. Therefore, the search for neuroprotective agents remains relevant. The aim of the research is to evaluate the neuroprotective effect of citicoline in conditions of acute reversible cerebral ischemia in rats. Material and methods. The study involved 79 male Wistar rats, 65 of which underwent 20-minute subtotal reversible cerebral ischemia by simultaneous bilateral ligation of the internal carotid arteries. The animals were divided into 3 groups: 1st - sham-operated rats; 2nd – rats with ischemia-reperfusion modeling without treatment (control group); 3rd - rats which were administered intravenously once with the drug citicoline immediately after ischemia-reperfusion modeling. The dynamics of lethality and neurological status were assessed. The functional state of the central nervous system was determined using the "open field" test. Changes in biochemical parameters (glucose, lactate, succinate dehydrogenase, malondialdehyde, superoxide dismutase, total NO synthase activity) in the somatosensory cortex were analyzed. Results. In the group 3 mortality was significantly lower than in the control group at the 1th, 12th, and 24th hours of an observation (0%, 24% and 32%). Citicoline significantly reduced neurological deficits in the subacute and recovery periods of the acute ischemic injury (according to the McGraw Stroke-index scale). The citicoline use led to an increase in the duration of the horizontal locomotor activity episodes by an average of 70,0%. Its use also significantly reduced an increase in glucose and lactate levels in the somatosensory cortex on the day 7 by an average of 17,5% and 32,0%, on the day 14 - by 10,1% and 41,1%, when the succinate dehydrogenase level remained 2 times higher, and the malondialdehyde level was lower on average by 55,6% than in rats of the group 2 (p<0,05). Also, on the experimental day 7 an increase in the total activity of NO synthase was recorded in the group 3 by an average of 11,1%, and in the group 2 by 82,4%, when on the day 14 – 10,0% and 72.0% (p<0,05) respectively. Conclusions. Intravenous administration of citicoline in cerebral ischemia was accompanied by plus dynamics in neurological status, better survival of animals, and normalization of pathobiochemical changes in the somatosensory cortex of a brain in rats, which allows including this agent to secondary neuroprotectors.