Comparative effects of mesenchymal stromal cells of various origins and sources on biochemical parameters in the hippocampus of rats during cerebral ischemia-reperfusion

Abstract

In neurodegenerative processes of the brain, the hippocampus is primarily damaged with subsequent cognitive impairments as a result of increased generation of reactive oxygen species and reactive nitrogen species, which lead to apoptosis and necrosis of neurons. Cell therapy with the use of mesenchymal stromal cells (MSCs) has shown encouraging results regarding endogenous mechanisms of neuroregeneration in response to ischemic injury of brain structures. The work aimed to study the therapeutic potential of MSCs of various origins and sources, MSCs lysate and reference drug citicoline on the energy component of neuronal metabolism, oxidative and nitrosative stress in the rat hippocampus under conditions of cerebral ischemia-reperfusion (IR). Material and methods. The experiment was carried out on 126 Wistar rats with modeled pathology (20-minute IR of the internal carotid arteries), which were injected with MSCs derived from Wharton’s jelly of the human umbilical cord, MSCs derived from human and rat adipose tissues, rat embryonic fibroblasts, MSCs lysate and citicoline immediately after removal of the ligatures. Biochemical parameters of carbohydrate metabolism (glucose, lactate), oxidative (NADPH oxidase activity) and nitrosative stress (NO synthase activity) in the rat hippocampus were determined on days 7 and 14 after IR under the conditions of cerebral IR and on the background of its correction. Results. It was established that during IR in the rat hippocampus of the brain, the content of glucose and lactate increases, the process of aerobic oxidation of glucose is inhibited, anaerobic glycolysis increases, lactic acidosis develops in hippocampal cells, the level of NADPH oxidase activity decreases, and an imbalance occurs in the functioning of the nitrogen monoxide system. A positive effect of human umbilical cord Wharton’s jelly-derived MSC and rat embryonic fibroblasts transplantation, and the use of citicoline on the stabilization of glucose, lactate, NADPH-oxidase and nitric oxide levels was found. Transplantation of human and rat adipose-derived MSCs was significantly less effective than citicoline and demonstrated no statistically significant modulatory effect on biochemical parameters in the hippocampus of experimental animals with IR. Conclusions. Transplantation of the human umbilical cord Wharton’s jelly-derived MSCs was not inferior to the citicoline and, better than other tested MSCs and their lysate, contributed to the recovery of disturbed energy processes (glucose level) and eliminated metabolic acidosis (lactate level) in the hippocampus of rats, i.e. had a positive modulating effect on the oxidant-antioxidant balance (NADPH oxidase activity level).