Mechanisms of Axonal Damage and Repair after Central Nervous System Injury

Central nervous system (CNS) injury initiates spatial and temporal neurodegeneration. Under pathologic conditions, damaged glial cells cannot supply sufficient metabolites to neurons, leading to energy deficiency for neuronal axons. The widespread disruption of cellular membranes causes disturbed intracellular signaling via dysregulated ionic gradients in neurons. Although several deleterious cascades are activated during the acute phase of CNS injury, some compensatory responses may tend to promote axonal repair during the chronic/remodeling phase. Because it may not be easy to block all multifactorial neurodegenerative pathways after CNS injury, supporting or boosting endogenous regenerative mechanisms would be an important therapeutic approach for CNS diseases. In this mini-review, we briefly but broadly introduce basic mechanisms that trigger axonal degeneration and then discuss potential targets for promoting axonal regeneration after CNS injury.