The influence of mesenchymal stromal cells of different genesis on energy metabolism in the rat somatosensory cortex during ischemia-reperfusion modeling

Abstract

Introduction. About 60-80% of cerebral circulation disorders are due to ischemia, that leads to high mortality, disability in working age and economic burden on society in developed countries of the world. Objective: To investigate the effect of ischemia-reperfusion on parameters of carbohydrate and energy exchanges in the rat somatosensory cortex and to determine the cerebroprotective action of mesenchymal stromal cells (MSCs)of various genesis, MSC lysate and the reference drug Citicoline. Methods. The study was performed on 200 male Wistar rats, divided into 9 groups. Group 1 included intact animals; group2–sham-operated rats; group3–control pathology (rats were subjected to ischemia-reperfusion by occlusion of the internal carotid arteries and injected with a 0.9% saline solution(2 ml/kg)into the femoral vein); group4–immediately after ischemia-reperfusion rats were transplanted with 106MSC cells/animal derived from Wharton’s jelly of the human umbilical cord; group5–106cells/animal of rat embryonic fibroblasts; group6–106cells/animal derived from human adiposeMSCs; group7–106cells/animal derived from rat adipose MSCs; group 8 –0.2 ml/animal of lysate derived from Wharton’s jellyMSCs; group9–the reference drug Citicoline(250 mg/kg). Parameters of carbohydrate and energy metabolism in rat somatosensory cortex under the conditions of cerebral IR and on the background of correction studied on the 7th and 14th day. Results.It was found that after cerebral ischemia-reperfusion in the rat somatosensory cortex in research periods an increase in the levels of glucose, lactate, lactate/pyruvate ratio and a decrease in the content of pyruvate and succinate dehydrogenase were revealed. In the groups of experimental animals with intravenous transplantation of MSCs of various origins, MSC lysate and Citicoline, the perturbation in glucose metabolism was reduced, lactate content was decreased and the levels of pyruvate and succinate dehydrogenase were significantly increased (p<0.05), compared to rats with control pathology. A more pronounced positive effect in the recovery of disturbed energy processes and elimination of metabolic acidosis was observed with the use of human Wharton’s jelly-derived MSCs. Conclusions. The study demonstrated that experimental 20-minute model ischemia-reperfusion in rats caused a violation of the carbohydrate and energy balance in the somatosensory cortex. Human umbilical cord blood-derived MSCs contributed to the recovery of disturbed energy processes in the somatosensory cortex and eliminated metabolic acidosis at the level of Citicoline or better than it, which is one of the links of the mechanism of the cerebral protective action of MSCs. Embryonic rat fibroblasts were slightly inferior in efficiency to Citicoline and human umbilical cord Wharton’s jelly MSCs, which indicates a higher cerebroprotective activity of xenotransplantation.