Peripheral nerve injury, repair, and regeneration

Abstract

Injuries to the peripheral nervous system (PNS) present a serious health problem for society, affecting approximately 2.8% of all trauma cases, often resulting in poor recovery of function and subsequent impaired quality of life for the patient (McAllister et al. 1996, Noble et al. 1998, Belkas et al. 2004, Lundborg 2004). For example, approximately 360,000 people in the United States alone suffer from paralytic syndromes of the upper extremity annually, resulting in 8,648,000 and 4,916,000 restricted activity and bed/disability days respectively (Kelsey et al. 1997). Approximately 100,000 patients undergo neurosurgical procedures of the PNS in the United States and Europe annually (Schlosshauer et al. 2006). The majority of patients with PNS injury has both motor and sensory deficits and often suffer from neuropathic pain. In contrast to the central nervous system (CNS), the PNS may exhibit spontaneous regeneration, albeit over shorter distances, with poor recovery of function being particularly prevalent in injuries that completely sever nerves from their targets. The healing of nerve injuries is unique in that it is a process of cellular repair as opposed to tissue repair (Lundborg and Danielsen 1991). Transected axons (Fig. 10.1) must redeem their original axoplasmic volume by extending processes distally, concomitant with the surrounding microenvironment. Transection of peripheral nerves results in Wallerian degeneration in all axons distal to the injury site, evidenced by the disintegration of axoplasmic microtubules and neurofilaments (Seckel 1990). The majority of axons along the distal stumps of transected nerves are reduced to granular and amorphous debris within 24 h; by 48 h, the myelin sheath transforms into short segments to form ovoids (Chaudhry et al. 1992). Activated macrophages invade the degenerating distal nerve stump and phagocytose the disintegrating nerve fibers and myelin. There is an accompanying proliferation of Schwann cells, resulting in the formation of longitudinal Schwann cell bands (bands of Bungner), as they divide and remain within the basal lamina lined endoneurial tubes. Proximal to the injury site where the axons are still intact, both myelinated and unmyelinated fibers spontaneously sprout new axons, forming a "regenerating unit" that is surrounded by a common basal lamina (Lundborg 2004). Axonal sprouts, facilitated by laminin, proceed in a distal fashion, as they establish an intimate relationship with axons and proliferating/migrating Schwann cells (Chen et al. 2005). Clinical treatment of peripheral nerve injuries focuses on proximally regenerating axons into distal endoneurial tubes, which ultimately leads to specific end-organ re-innervation. Unfortunately, the clinical treatment of peripheral nerve injuries has changed relatively little over the past 30 years, despite considerable advances in our understanding of the neurobiology of nerve regeneration (Belkas et al. 2004). The following sections detail current clinical methods of nerve repair and nerve reconstruction management. © Springer Science+Business Media, LLC 2009.