Abstract: After central nervous system (CNS) injury, severed axons fail to regenerate and their disconnections to the original targets result in permanent functional deficits in patients (Mahar and Cavalli, 2018). Both the diminished intrinsic regenerative capacity of mature neurons and the inhibitory CNS milieu contribute to the regenerative failure following CNS injury. Glial cells have important physiological functions, including maintaining homeostasis, supporting and protecting neurons, regulating neuronal activities, and forming myelin (Gaudet and Fonken, 2018). In response to CNS injury, reactive glial cells shift their phenotype and activities and contribute to scar formation. Gliosis is a defense response of the CNS to diminish primary damage and to repair injured tissues and has numerous beneficial effects, such as preventing the spread of damage from injury site. Various glia present around the lesion, including astrocytes, may express multiple positive molecules that promote axon regrowth, such as laminins, syndecans, glypicans, and decorin. Accordingly, preventing scar formation after injury or removing chronic astrocytic scars failed to promote axon regeneration (Anderson et al., 2016). However, reactive glial cells and scar tissues ultimately produce detrimental effects by upregulating numerous molecules that suppress neuronal elongation and form potent barriers to axon regeneration. Shortly after CNS injury, chondroitin sulfate proteoglycans (CSPGs) are upregulated dramatically and form part of the extracellular matrix components. CSPGs remain around the lesion epicenter for at least months, form an inhibitory milieu around the lesion, and suppress regrowth of injured axons into and beyond the lesion area (Hara et al., 2017). Two transmembrane protein tyrosine phosphatases (LAR and PTP σ) are important for mediating inhibition by CSPGs.