On the basis of a comprehensive study the dissertation presents the theoretical generalization and a new approach to solving scientific problem of spasticity pathogenesis and restorative treatment of spinal cord injury. The research has been conducted over albino outbred rats of different age and sex (n=287; 23 experimental groups), model of injury - left-side spinal cord hemisection at Т11 level. The research proposes a model of spinal cord compression by the biologically compatible foreign body, model of temporary cerebellar hypotonia. The author has examined as regenerative neuro-engineered interventions three types of immediate tissue transplantation into the injury zone, 2 different proregenerative matrix implantation, three types of transplantation of macroporous hydrogel matrix (NeuroGel), associated with stem cells. The behavioral (ВВВ-scale), clinical (Ashworth-scale), electrophysiological, cellular electrophysiological, tissue culturing, molecular, immunological, pathomorphological, mathematical and statistical research has been conducted. Compression of the spinal cord by biologically compatible foreign body significantly worsens the course of the regeneration process; during the first 8 weeks the ipsilateral hind limb function indicator (IHL FI) in animals of the group is the lowest one - 1,30±0,94 points of the BBB-scale; during the 3rd-4th month BI LFI veraciously increases till 2,35±0,95 points of the BBB-scale, which is likely due to the change in the form of a foreign body and its utilization, decrease of the pressure on the spinal cord. At the 24th week of the observation BI LFI was 2,35±0,95 points of the BBB-scale. Reducing the spinal cord compression even at the late period of injury significantly improves the efficiency of the regeneration process. Spasticity is associated with the dorsal horn hyperexcitability resulting from an increase in excitation and disinhibition occurring in two respective types of sensory interneurons. In the tonic-firing inhibitory lamina II interneurons, glutamatergic drive was reduced while glycinergic inhibition was potentiated. In contrast, excitatory drive was boosted to the adapting-firing excitatory lamina II interneurons while GABA-ergic and glycinergic inhibition was reduced. Thus, increased activity of excitatory interneurons coupled with the reduced excitability of inhibitory interneurons post-SCI could provide a common mechanism for chronic pain and spasticity after spinal cord injury. Expression of the matrix RNA (mRNA) proteins Gria1-4, Slc18a2, Slc32a1, Dbh, Tph2, Ptf1a in a lumbo-sacral rat spinal cord matter in 6 weeks after injury was investigated using a PCR method in a real time. Low expression of the tryptophan-hydroxylase 2 (Tph2) and dopamine-?-hydroxylase (Dbh) mRNA was noted in tissue of the intact spinal cord. A spinal cord trauma сauses essential lowering of the Tph2 mRNA expression - homolaterally, and of transmembrane carrier of monoamines Slc18a2 - contralaterally, while in the receptor of glutamate Gria3 subunit - bilaterally. Lateralization is not confirmed by immediate comparison of results of contralateral halves of a spinal cord. Lateralized laminectomy without a spinal cord trauma causes significant bilateral raising of the Gria2 expression in a spinal cord tissue. The data obtained do not correlate with the function indices and spasticity changes of posterior extremities. The maximum value of the IHL FI after transplantation has been observed at the level of (3,6±0,5) points ВВВ). Significant differences between the IHL FI values of the groups ТОBT, TFСT and TFKT have not been observed during the experiment. A common feature of the dynamics of the three experimental groups is prevalence of IHL FI values over the control during the first few weeks and lack of progression during further period of observation. The increase (p<0.05) of spasticity index was recorded in the control groupe during the period of 1st-2nd and 5th months, in the groupe TOBT - during the period of 1st-2nd and 6th month, in the groupe TFCT - during the 3rd week, in the groupe TFKT - during the 2nd week. At the 7th day rate of spasticity in the TFCT and TFKT reached 1 point of Ashworth scale, in the TOBT and control groupe - was at 0 point. Within 2nd-4th weeks noted a high (TFСT, TFKT), intermediate (control groupe) and low (TOBT) level of spasticity. The level of spasticity in the groups TFСT and TFKT exceeded (p<0.05) the indicator of control groupe during the 1st-3rd and 1st-2nd weeks, respectively. The level of spasticity in the group TOBT conceded (p<0.05) values of the control group (2nd week), TFСT (1st-6th week) and TFKT (1st-3rd week). At the 24th week of observation level of spasticity in experimental groups was 2.6±0.4 (control groupe), 2.2±0.2 (TOBT), 2.1±0.3 (TFСT) and 1.9±0.3 (TFKT). In 59 % of the animals in the groupe TOBT noted early debut of spasticity with flexion-adduction installation in hip and knee and peripheral paresis (hypotonia/atony) at the ankle joint. Similar spastic installation was noted in 40 % of the animals in the groupe TFСT (for 2nd month) and 25 % of the animals in the groupe TFKT (during 1st-2nd week). In the control group signs of severe neurogenic pain in the remote period was found in 19 % of animals, in the group TOBT - in 27 %, in the groupe TFСT - in 6 % (1 animal), in the groupe TFKT - was not observed. In general, approved types of neurotransplantation exert significant influence on the course of spasticity syndrome; the mechanisms of influence related to the cellular structure, angiogenic and immunogenic properties of the grafts. Neural stem cells, bone marrow stem cells and neural crest stem cells xenotransplantation in association with macroporous hydrogel matrix provide recovery of motor function of paretic limb to a level ~ 13 points, exceeding the reference value by 4 times, it provides for a tendency towards potentiation of the NeuroGel positive impact on the course of the spinal cord injury, efficiency of this influence significantly depends on the sex of recipient and donor organism. Restriction of spontaneous locomotor activity slows paretic limb motor function recovery during 1st month, reduces the duration of significant recovery in the late period of injury, accelerates the formation of stable spasticity syndrome. In the stratum of matrix, implanted in association with stem cells, strong prolifirations of fibers of recipient spinal cord are being formed, including varicose axon branches; transplanted cells are stored for at least 7 months and differentiated by neuronal phenotype. In the dynamics of observation most experimental groups, except foreign body implantation and olfactory bulb tissue transplantation, are characterized by the absence or positive correlation between the mean values of function and spasticity.
