Energy metabolism and metabolite changes in the brain of rats with experimental allergic encephalomyelitis under the influence of cryoextracts of placenta and spleen, and conditioned medium of mesenchymal stem cells
Authors: Hladkykh F.V. , Liadova Т.І. , Matvieienko М.S. 
Published: February 2025

Background. Multiple sclerosis (MS) is a global issue with increasing prevalence. 0–15% of people with MS have progressive disability from the onset, usually due to spinal cord involvement. The range of available treatments for patients with MS is continually expanding as researchers seek new ways to improve the effectiveness and safety of therapy. The brain, accounting for only 2% of the total body mass, consumes approximately 20% of the oxygen and 25% of the glucose taken in by the human body, indicating an extremely high metabolic rate.

Purpose – to characterize the state of energy metabolism and metabolic changes in the brain of rats with experimental allergic encephalomyelitis (EAE) in the context of the administration of placental and spleen cryoextracts, as well as mesenchymal stem cell-conditioned medium.

Materials and Methods. EAE in rats was induced by administering an encephalitogenic emulsion containing complete Freund’s adjuvant and a homogenate of allogeneic brain. The content of adenyl nucleotides – adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) – was studied in deproteinized brain homogenate using chromatographic methods. The content of lactate, pyruvate, and malate was determined spectrophotometrically.

Results. In rats with EAE, the level of lactate in the brain was significantly elevated (4.40 ± 0.13 μmol/g) compared to intact animals (2.24 ± 0.13 μmol/g, p < 0.001). Treatment with placental cryoextract and stem cell-conditioned medium led to a decrease in lactate levels to 3.27 ± 0.10 μmol/g (p < 0.001) and 3.00 ± 0.16 μmol/g (p < 0.001), respectively. The level of pyruvate decreased by 54.1% in the control group but increased after the administration of placental cryoextract (p < 0.001), although it remained below normal. Treatment with spleen cryoextract and stem cell-conditioned medium promoted an increase in pyruvate levels, but the effect was less pronounced. In the control group, malate decreased by 50% (p = 0.001), but after treatment with placental cryoextract, the malate level increased to 0.30 ± 0.03 μmol/g (p = 0.024). The lactate-to-pyruvate ratio was significantly elevated in the control group rats (16.3 [14.3; 32.0] μmol/g), and treatment with stem cell-conditioned medium most effectively reduced this ratio to 11.0 [8.0; 11.3] μmol/g tissue (p < 0.001).

Conclusions. Metabolic changes in rats with EAE indicate disturbances in the energy processes in brain cells, manifested by increased lactate levels, decreased pyruvate and malate levels, and activation of anaerobic metabolism. Treatment with placental and spleen cryoextracts and stem cell-conditioned medium improved energy processes, particularly by reducing lactate levels and the lactate-to-pyruvate ratio, as well as partially restoring energy indicators. The most pronounced effect was observed with the use of stem cell-conditioned medium, showing significant restoration of energy balance and potential for treating EAE-induced disorders.