Table 1.

Injury mechanism and confronted repair challenges of the PNS and the CNS.

Scenario	Injury mechanism	Repairing challenges	Refs
PNS	1.Wallerian degeneration of the distal part of the axon resulting in fragmentation and disintegration of the axon in the first 18–48 ​h. 2.Proinflammatory cytokines secretion: tumor necrosis factor-alpha (TNF-α) and interleukin-1-alpha (IL-1α). 3.Removal of axonal and myelin debris by macrophages and SC. 4.Interleukin-1 (IL-1) and platelet-derived growth factor stimulates SC to divide, de-differentiate, and proliferate distal to the injury. 5.Stimulated SC to secrete growth factors such as nerve growth factor or insulin-like growth factor-1. 6.Band Büngner formation guiding axon and growth cones to reconnect from proximal end to distal end across the gap.	1.Long-distance regeneration (> 10 ​mm). 2.Re-establishment of appropriate connections between the periphery and the central nervous system.	[8,44]
CNS	1.Wallerian degeneration in the damaged tracts. 2.Degeneration of myelin and axonal debris after the apoptosis of oligodendrocytes. 3.Inhibitory neurite growth molecules in myelin: Nogo-A, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein. 4.Glial scar formation is initiated by astrocytes with inhibitory molecules such as proteoglycans.	1.Modulation of inhibitory microenvironment for axonal regeneration in the lesion site. 2.Collaborative participation of distinct cell types for ideal axonal regeneration. 3.Aligned distribution of neuronal cells to form orientational nerve bundles. 4.Speeded reinnervation time being the most important determinant of successful clinical outcomes.	[45,46]