Peripheral Nerve Regeneration

Abstract

The nerve chamber model has dominated the experimental study of peripheral nerve (PN) regeneration with animal models as well as in several clinical applications, such as the treatment of paralysis of limbs following severe trauma. The two stumps resulting from nerve transection are inserted inside a tubular chamber made from one of several materials, occasionally filled with various substances, and the quality of the reconnected nerve is assayed. Recent use of methods for data reduction has led to generation of a large normalized database from independent investigations. Methods for data normalization (reduction) are based on systematic use of the critical axon elongation, Lc, the gap length between the transected stumps at which the frequency of reconnection is just 50% for a given configuration. Four theories are compared for their ability to explain the normalized data. Although the neurotrophic and contact guidance theories explain some of the data, combined use of the more recent microtube theory and pressure cuff theory appears capable of explaining a much larger data set. PN regeneration appears to be upregulated by chamber configurations that facilitate formation of basement membrane microtubes about 10-20 microm in diameter, comprising linear columns of Schwann cells surrounded by basement membrane, into which axons elongate and eventually become myelinated. Regeneration is downregulated by experimental configurations that permit formation of a contractile cell (myofibroblast) capsule around the regenerating nerve that appears to restrict growth of a nerve trunk by application of circumferential mechanical forces. These two processes work competitively to regulate nerve regeneration in the chamber model.