Evaluation of the Effectiveness of Systemic Therapy of Spinal Cord Injury of Moderate Severity with Human Umbilical Cord Placental Blood Mononuclear Cells Using Indicators of Dispersion of Articular Angles in the Swimming Test.

Female Sprague-Dawley rats were used as models of moderate contusion spinal cord injury to evaluate the efficiency of single systemic (intravenous) infusion of human mononuclear cord blood cells for restoration of the motor function of hind limbs. The dynamics of recovery of hind limb motor function was assessed using a specially designed method based on calculation of selective dispersion and amplitude-dependent dispersion of hind limbs joint angles measured in the swimming test. The obtained data suggest that systemic application of human mononuclear cord blood cells significantly (p<0.05) promoted recovery of hind limb motor function in the animal models of contusion spinal cord injury of moderate severity in comparison with control animals (without cell therapy).

A Method of Assessment of the Motor Function of Hind Limbs by Swim Test in Spinal Cord Injury Models.

In most studies, various load tests are used to assess the recovery of functions after spinal cord injury in animals. However, the existing methods of assessing the movement in animals are not sufficiently accurate and objective. We developed a new method for assessing motor activity of laboratory animals that allows objective and highly accurate evaluation of movements in animals with serious neurological disorders caused by spinal cord injury. The swimming test was used as the main load test. Motor activity of swimming animals was assessed by measuring angles relative to the axis of motion, and the degree of angle spread for each joint and limb was estimated using the dispersion parameters depending on the values of the angles of the joints and the dispersion depending on the amplitudes of the angles. In Sprague-Dawley rats, contusion of the spinal cord at the Th9 level was modeled. In the swimming test, healthy control animals showed stability of both variance indicators over 6 weeks. In rats with spinal cord injury, motor activity of the hind limbs tended to increase from the first to the third weeks and remained at this level from the third to sixth weeks. The results suggest that the proposed method can become a good analogue of modern methods for assessing motor activity.

Comparison of the Efficiency of Systemic and Local Cell Therapy with Human Umbilical Cord Blood Mononuclear Cells in Rats with Severe Spinal Cord Injury.

Rat model of severe contusion spinal cord injury was used to study the effect of single intravenous and intraspinal injection of human umbilical cord blood mononuclear cells on the restoration of motor function of the hind limbs. Recovery of the motor function of the hind limbs was assessed using load tests and open-field test according to BBB scale. Cell injection via both routes significantly improved (p≤0.05) the recovery of the motor function of the hind limbs by 35-40% relative to the level of "self-recovery"; the effects of intravenous andintraspinal administration did not differ significantly.

Collagen Implant and Mononuclear Cells of Umbilical Blood Allow the Restore of Movements of Hind Limbs after Removing the Site of Spinal Cord.

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.

Thiamine Induces Long-Term Changes in Amino Acid Profiles and Activities of 2-Oxoglutarate and 2-Oxoadipate Dehydrogenases in Rat Brain.

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.

Efficiency of transplantation of human placental/umbilical blood cells to rats with severe spinal cord injury.

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.

[Protective action figurations for superoxide dismutase - chondroitin sulfate - catalase bienzyme conjugate after its medicative administration in endotoxin shock]. / Pokazateli zashchitnogo deistviia bifermentnogo kon"iugata superoksiddismutaza-khondroitinsul'fat-katalaza posle ego lechebnogo vvedeniia pri éndotoksicheskom shoke.

Previously it found that the bienzymatic conjugate superoxide dismutase-chondroitin sulfate, catalase (SOD-CHS-CAT) increased the survival rate of rats with endotoxic shock caused by the administration of lipopolysaccharide (LPS). This effect was observed both in preventive (before LPS) and therapeutic conjugate administration (after the administration of LPS). This study shows that the development of endotoxic shock is accompanied by increased levels of NO in the liver, lungs, kidneys, heart; administration of the SOD-CHS-CAT conjugate insignificantly influenced this parameter. At the same time, the changes in blood urea and creatinine suggest the protective effect of the conjugate on renal function, while diverse changes in biochemical parameters studied complicate the formation of the agreed conclusions on the state of other organs.