Abstract
The repair of severe nerve injuries requires an autograft or conduit to bridge the gap and avoid axon dispersion. Several conduits are used routinely, but their effectiveness is comparable to that of an autograft only for short gaps. Understanding nerve regeneration within short conduits could help improve their efficacy for longer gaps. Since Schwann cells are known to migrate on endothelial cells to colonize the “nerve bridge”, the new tissue spontaneously forming to connect the injured nerve stumps, here we aimed to investigate whether this migratory mechanism drives Schwann cells to also proceed within the nerve conduits used to repair large nerve gaps. Injured median nerves of adult female rats were repaired with 10 mm chitosan conduits and the regenerated nerves within conduits were analyzed at different time points using confocal imaging of sequential thick sections. Our data showed that the endothelial cells formed a dense capillary network used by Schwann cells to migrate from the two nerve stumps into the conduit. We concluded that angiogenesis played a key role in the nerve conduits, not only by supporting cell survival but also by providing a pathway for the migration of newly formed Schwann cells.
Highlights
Blood vessels were shown to provide a track for Schwann cell migration [6], a process that is necessary for axonal pathfinding across the nerve bridge [7]
To investigate the regeneration of peripheral nerves within nerve conduits, rat median nerves were injured and 8 mm nerve gaps were repaired with a 10 mm chitosan conduit
Since vascular endothelial growth factor-A (VEGF-A) is known to play a key role in angiogenesis and nerve bridge formation [6], we investigated its expression within the chitosan conduit using quantitative expression analysis on samples obtained 7, 14, 21, and 28 days after the injury and repair
Summary
When the gap is a few millimeters, the formation of a 3D structure characterized by a matrix, fibroblasts, perineurial, and inflammatory cells called the “nerve bridge” between the proximal and the distal stump was observed [4,5,6] Within this 3D structure, macrophages sensing a hypoxic condition produce and secrete vascular endothelial growth factor-A (VEGF-A), which, through a chemotactic signal, guides endothelial cell proliferation and vessel formation [6]. Schwann cell migration is necessary for axonal pathfinding in the nerve bridge, but it is one of the intrinsic steps required for nerve regeneration for all nerve injuries, regardless of the type of damage and repair [8,9]
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