Spinal cord injury: pathogenetic principles of molecular and cellular therapy

Abstract

Spinal cord injury is a prognostically unfavorable condition due to the subsequent development of primary and secondary damage to the nervous structures, leading to various disorders of motor and sensory capabilities, which is also accompanied by dysfunction of the autonomic nervous system. Considering the initial complexities of regeneration processes in the central nervous system, in order to select treatment tactics for patients with spinal cord injury, it is important for doctors to know the cellular basis of the pathophysiological processes occurring in the spinal cord in the acute and chronic phases after injury, including in order to adequately select cells-targets of pharmacological drugs. Existing methods of treating neurotrauma can still do little to help prevent the death of neurons and the formation of glial scars, which make it impossible for the migration of cells involved in the processes of post-traumatic remodeling of the spinal cord and become an obstacle to the sprouting of regenerating axons. Unfortunately, preventing the formation of a glial scar remains an unsolved problem in clinical practice. In addition, in the case of spinal cord injuries in the clinic, it is extremely important to provide humoral stimulation to maintain the viability of nerve structures, for example, using numerous growth factors that are well known today, which have a beneficial effect on the intracellular regeneration of neurons and other cells involved in these processes, but the methodology for their delivery into the central nervous system has only been tested in animal models. That is why there is an urgent need to develop fundamentally new approaches to the treatment of the consequences of spinal cord injury, including cellular technologies based on transplantation of stem or differentiated cells in order to restore nerve structures and secretion of growth factors, the use of genetic constructs carrying genes for neurotrophic factors that can minimize development of post-traumatic destructive processes in the central nervous system. This review is devoted to these issues.