Regenerating axons are not required to induce the formation of a Schwann cell cable in a silicone chamber.
After suture of proximal and distal nerve stumps into the ends of a silicone chamber, a tissue cable forms inside the chamber through which axons regenerate. Schwann cells are a critical cellular component of the cable because in their absence axons fail to regenerate into the cable. In this study, we sought to determine whether axons were needed to induce the formation of a Schwann cell-containing cable. Transected stumps of sciatic nerves of adult rats were sutured into the ends of silicone chambers prefilled with phosphate-buffered saline or dialyzed plasma, leaving a 10-mm interstump gap. In order to eliminate any axonal influence in the chamber, the proximal sciatic nerve was further transected, ligated, and reflected, leaving a 4-mm piece of denervated nerve in the proximal chamber. A tissue cable formed at 4 weeks only in those chambers prefilled with dialyzed plasma. Light and electron microscopy revealed a central core of Schwann cells and fibroblasts within the cable that were collectively surrounded by a circumferential layer of fibroblasts and collagen. Blood vessels were randomly located throughout the cable. The Schwann cells extended numerous processes that were confined within a basal lamina-like membrane. Many of these processes contained microtubules and resembled unmyelinated axons. The ultrastructure of the processes, however, differed from that of axons in that some of the processes were in direct contact with the basal lamina of the Schwann cells and not surrounded by any other cell extensions. However, since these processes neither stained with silver nor disappeared after transection of the nerves entering or leaving the chamber, we conclude that they are not axons but in fact Schwann cell processes. In other animals bearing 4-week cables, the reflected nerve stump was reattached to the nerve piece in the proximal end of the chamber. Four weeks later, all the cables and varying lengths of the distal nerve trunks were filled with numerous myelinated and unmyelinated axons. The Schwann cell cable that forms within a dialyzed plasma prefilled chamber presents a useful system for basic research concerning the molecular mechanisms of Schwann cell or Schwann cell-axonal interactions and for applied research involving the clinical repair of human peripheral nerve injuries. Since a cable formed by our surgical method supports axonal regeneration, it has the potential to eliminate the need for a nerve graft to repair a gap in a nerve that requires delayed surgical intervention.
Williams
L R
LR
CNS Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
Azzam
N A
NA
Zalewski
A A
AA
Azzam
R N
RN
D000818:Animals; D002455:Cell Division; D003714:Denervation; D005260:Female; D008854:Microscopy, Electron; D009416:Nerve Regeneration; D009462:Neurology / Q000295:instrumentation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000166:cytology; D012828:Silicones; D014855:Wallerian Degeneration
D012828:Silicones