Motor tract reorganization after acute central nervous system injury: a translational perspective

Acute central nervous system injuries are among the most common causes of disability worldwide,with widespread social and economic implications.Motor tract injury accounts for the majority of this disability;therefore,there is impetus to understand mechanisms underlying the pathophysiology of injury and subsequent reorganization of the motor tract that may lead to recovery.After acute central nervous system injury,there are changes in the microenvironment and structure of the motor tract.For example,ischemic stroke involves decreased local blood flow and tissue death from lack of oxygen and nutrients.Traumatic injury,in contrast,causes stretching and shearing injury to microstructures,including myelinated axons and their surrounding vessels.Both involve blood-brain barrier dysfunction,which is an important initial event.After acute central nervous system injury,motor tract reorganization occurs in the form of cortical remapping in the gray matter and axonal regeneration and rewiring in the white matter.Cortical remapping involves one cortical region taking on the role of another.cAMP-response-element binding protein is a key transcription factor that can enhance plasticity in the peri-infarct cortex.Axonal regeneration and rewiring depend on complex cell-cell interactions between axons,oligodendrocytes,and other cells.The RhoA/Rho-associated coiled-coil containing kinase signaling pathway plays a central role in axon growth/regeneration through interactions with myelin-derived axonal growth inhibitors and regulation of actin cytoskeletal dynamics.Oligodendrocytes and their precursors play a role in myelination,and neurons are involved through their voltage-gated calcium channels.Understanding the pathophysiology of injury and the biology of motor tract reorganization may allow the development of therapies to enhance recovery after acute central nervous system injury.These include targeted rehabilitation,novel pharmacotherapies,such as growth factors and axonal growth inhibitor blockade,and the implementation of neurotechnologies,such as central nervous system stimulators and robotics.The translation of these advances depends on careful alignment of preclinical studies and human clinical trials.As experimental data mount,the future is one of optimism.

A radical scavenger edaravone and oligodendrocyte protection/regeneration

Cerebral white matter is vulnerable to oxidative stress： Oxidative stress is one of the major harmful conditions for the central ner- vous system （CNS）. Oxidative stress is a state from an imbalance between free radical production and their removal by antioxidants, resulting in an excessive amount of reactive oxygen species （ROS） in cells and tissues. ROS causes cell damage due to oxidation of cellular components, including DNAs, proteins, and lipids. During physiological conditions, small amounts of ROS are generated in the process of normal biological activity, and ROS at physiological levels play important roles in maintaining cellular homeostasis （Chen et al., 2018）. However, during pathological conditions, ROS levels are increased and excessive ROS can lead to deleterious ef- fects on many kinds of cells.