Molecular mechanisms of long-term changes in brain metabolism after thiamine administration (single i.p. injection, 400 mg/kg) were investigated. Protocols for discrimination of the activities of the thiamine diphosphate (ThDP)-dependent 2-oxoglutarate and 2-oxoadipate dehydrogenases were developed to characterize specific regulation of the multienzyme complexes of the 2-oxoglutarate (OGDHC) and 2-oxoadipate (OADHC) dehydrogenases by thiamine. The thiamine-induced changes depended on the brain-region-specific expression of the ThDP-dependent dehydrogenases. In the cerebral cortex, the original levels of OGDHC and OADHC were relatively high and not increased by thiamine, whereas in the cerebellum thiamine upregulated the OGDHC and OADHC activities, whose original levels were relatively low. The effects of thiamine on each of the complexes were different and associated with metabolic rearrangements, which included (i) the brain-region-specific alterations of glutamine synthase and/or glutamate dehydrogenase and NADP+-dependent malic enzyme, (ii) the brain-region-specific changes of the amino acid profiles, and (iii) decreased levels of a number of amino acids in blood plasma. Along with the assays of enzymatic activities and average levels of amino acids in the blood and brain, the thiamine-induced metabolic rearrangements were assessed by analysis of correlations between the levels of amino acids. The set and parameters of the correlations were tissue-specific, and their responses to the thiamine treatment provided additional information on metabolic changes, compared to that gained from the average levels of amino acids. Taken together, the data suggest that thiamine decreases catabolism of amino acids by means of a complex and long-term regulation of metabolic flux through the tricarboxylic acid cycle, which includes coupled changes in activities of the ThDP-dependent dehydrogenases of 2-oxoglutarate and 2-oxoadipate and adjacent enzymes.
The effects of a single intravenous injection of human umbilical blood were studied on the model of severe spinal cord contusion injury in rats. Rats receiving no umbilical blood (spontaneous recovery) served as the control. All rats exhibited pronounced hind limb paraplegia and autonomic dysfunction of pelvic organs after the injury. Recovery of the hind limb function was evaluated by loading tests and locomotor activity testing in the open field using BBB score for open-field testing. Testing was carried out weekly for 8 weeks after the injury. Open-field testing showed a significant (p < 0.05) increase of the rate and volume of the hind limb motor activity recovery in the groups receiving umbilical blood infusions.
Replacement of the removal site of the spinal cord on a collagen implant restores the motor function of the hind limbs in rats to the level of movements in the two joints for 8 weeks. After intravenous administration of mononuclear cells of human umbilical blood, recovery accelerated, significantly improved to the level of motion in the three joints, and there is a tendency to improve further recovery of movements.
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