Cellular migration and axonal outgrowth from adult mammalian peripheral nerves in vitro

Abstract

It is known that following peripheral nerve transections, sheath cells proliferate and migrate to form a bridge between nerve stumps, which may facilitate axonal regeneration. In the present investigations, cellular migration and axonal outgrowth from nerves of adult mice were studied in vitro using collagen gels. During the first 3 days in culture, profuse migration of fibroblasts and macrophages occurred from the ends of sciatic nerve segments, which had been lesioned in situ a few days prior to explantation, but not from segments of normal nerves. The mechanism of cellular activation in the lesioned nerves was not determined, but migration was blocked by suramin, which inhibits the actions of several growth factors. The migrating cells, which form the bridge tissue, may promote axonal regeneration in two ways. Firstly, axonal outgrowth from isolated intercostal nerves was significantly increased in co-cultures with bridges from lesioned sciatic nerves. This stimulatory effect was inhibited by antibodies to 2.5S nerve growth factor. Secondly, the segments of bridge tissue contracted when removed from animals. It is possible that fibroblasts within the bridge exert traction that would tend to pull the lesioned stumps of peripheral nerve together, as in the healing of skin wounds. The traction may also influence deposition of extracellular matrix materials, such as collagen fibrils, which could orient the growth of the regenerating axons toward the distal nerve stump.

Microtubule-Associated Protein 1B Controls Directionality of Growth Cone Migration and Axonal Branching in Regeneration of Adult Dorsal Root Ganglia Neurons

“…In preliminary experiments, we observed that neurites regenerating from the peripheral nerve stump were mostly longer than those growing from the dorsal root (see also Tonge et al, 1996). Thus, the following comparative analysis between wild-type and MAP1B-deficient DRG explants is based on fibers growing from the peripheral nerve.…”

Impaired Axonal Regeneration by Isolectin B4-Binding Dorsal Root Ganglion NeuronsIn Vitro

“…Because degenerating nerves of rats, mice, chickens, and frogs are known to release factors that stimulate neurite outgrowth from sympathetic ganglia and DRGs (Richardson and Ebendal, 1982;Windebank and Poduslo, 1986;Ferguson et al, 1989;Kuffler and Megwinoff, 1994;Tonge et al, 1996), we tested effects of media conditioned by segments of lesioned and normal nerves on explanted PN-DRG preparations to see whether stimulation of axonal outgrowth of IB4-labeled axons in collagen gels would occur. However, although we observed profuse outgrowth of PGP 9.5-positive axons in the collagen gels in media conditioned by peripheral nerve segments (which was primarily abolished by a neutralizing antibody to NGF), there was no stimulation of outgrowth of IB4-labeled axons.…”

The Effect of Collagen Nerve Conduits Filled with Collagen-Glycosaminoglycan Matrix on Peripheral Motor Nerve Regeneration in a Rat Model

“…The function of the axially aligned myofibroblasts is not fully understood. Axially aligned myofibroblasts may facilitate nerve regeneration by shortening the nerve gap 32 . These cells may be responsible for aligning newly synthesized collagen fibers and possibly regenerated axons during the healing process 31 .…”