The Potentiation of Peripheral Nerve Sheaths in Regeneration and Repair

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Exp Neurol. 2009 Jun 5.

The Potentiation of Peripheral Nerve Sheaths in Regeneration and Repair.

Muir D.

Department of Pediatrics, Neurology Division, McKnight Brain Institute,

University of Florida College of Medicine, Gainesville, Florida, USA.

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 peripheral

nerve sheaths play in regulating axonal regeneration and focuses on discoveries

leading to the inception and development of novel therapies for nerve repair.