Traumatic injury to the nervous system often results in life changing loss of neurological function. Spontaneous neural regeneration occurs rarely and the outcome of therapeutic intervention is most often unacceptable. An intensive effort is underway to improve methods and technologies for nervous system repair. To date, the most success has been attained in the outcomes of peripheral nerve restoration. The importance of the peripheral nerve sheaths in successful nerve regeneration has been long recognized. In particular, Schwann cells and their basal laminae play a central role in axon development, maintenance, physiology, and response to injury. The endoneurial basal lamina is rich in components that promote axonal growth. It is now evident that the bioactivities of these components are counterbalanced by various factors that impede axonal growth. The growth-promoting potential of peripheral nerve is realized in the degenerative processes that occur distal to a lesion. This potentiation involves precise spatiotemporal alterations in the balance of antagonistic regulators of axonal growth. Experimental alteration of nerve sheath composition can also potentiate nerve and improve key features of nerve regeneration. For instance, enzymatic degradation of inhibitory chondroitin sulfate proteoglycan mimics endogenous processes that potentiate degenerated nerve and improves the outcome of direct nerve repair and grafting in animal models. This review provides a perspective of the essential role that peripheral nerve sheaths play in regulating axonal regeneration and focuses on discoveries leading to the inception and development of novel therapies for nerve repair.
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