Spinal cord injury of various etiologies (injuries, malformations, inflammatory diseases, etc.) leading to motor disorders, dysfunctions of the visceral systems, cognitive and mental disorders, is an urgent medical and social problem. The method actively used in clinical practice is electrical stimulation of the spinal cord, however, a search for more effective approaches to combinatorial therapy is required. In previous studies (Musienko P et. al., 2011) it was shown that pharmacological effects on certain subtypes of monoamine receptors lead to improvement of specific parameters of motor function after severe spinal injury in rats. Simultaneous modulation of several receptors gives additional effects that exceed the result expected from a simple summation of the effects of individual components. Apparently, the observed phenomenon is the result of the combined activity of the injected neuroactive molecules.

The phenomenon of the combined action of drugs has been known for quite a long time, but drug combinations used in medical practice are often the result of accidentally discovered synergy, then adopted by doctors. The problem of combined pharmacotherapy has not been solved, there is no clear algorithmic approach to the search and creation of synergistically active drug combinations, which is relevant not only in neurorehabilitation, but also in other areas of medicine.
One of the key fundamental tasks of the group’s activity is the development of a methodology for the directed search for combinations of biologically active molecules (modulating various receptor systems), the effect of which is greatly enhanced due to the synergistic effect.

The practical goal of the group’s activity is to create a synergistically active complex of neuromodulators, the introduction of which will restore the pattern of motor activity in limbs immobilized due to spinal cord injury. It is also assumed that it will contribute to the activation of compensatory processes at the level of the organism as a whole. The complex will be formed mainly from existing drugs, the mechanism of biological action of which is mediated by the effect on various receptor systems. It may also contain components that play an important role in the regulation of compensatory processes in the body (regulatory peptides, neuroactive fatty acids).
The approach to solving the task set in the project involves a combination of various research methods that allow assessing the effect of the created complexes at different levels of the organization of the living. The initial selection of components will be based on the results obtained by methods of molecular modeling and analysis of drug databases. More accurate selection of components and their concentrations, evaluation of efficacy and toxicity — on cellular models. The effect on axon growth and regeneration will be investigated on models of primary neuron culture and on organotypic cultures of mammalian spinal cord sections. The assessment of the action of the neurocomplex at the level of the organism as a whole (including toxicity, behavior, regeneration, etc.) will be carried out on Danio rerio fish. The influence of the formed complexes on the restoration of motor functions after spinal injury (in vivo) in fish will be evaluated, as well as neuroplastic processes in the spinal cord and brain will be studied using histology and immunohistochemistry. The final stage of the research of the already formed neurocomplex will be the assessment of the transcriptomic response of fish and mammalian cells in the spinal cord injury model.