Electrically mediated regeneration and guidance of adult mammalian spinal axons into polymeric channels

An extracellular electric field has been shown to influence the regeneratio n of nerve fibers within the adult mammalian spinal cord. However, in these studies, few axons were labeled by local application of intracellular mark ers relative to the number of axons transected. This has limited an evaluat ion of the robustness of the response, and the direction of growth of regen erating axons that might be influenced by the orientation of the applied vo ltage gradient. In this study, a hollow silicone rubber tube (c. 6 mm x 1 m m outside diameter) containing a cathodal (negative) electrode was inserted longitudinally into the dorsal half of the adult guinea-pig spinal cord. T he electric field (similar to 100 mu V/mm) was imposed within the damaged s pinal cord with an implanted d.c. stimulator for about three weeks. Based o n previous studies, this orientation of the electric field would be expecte d to both initiate axonal regeneration and guide growing axons to, and into , the silicone guidance channel. In experimental animals (n = 20), a robust regeneration of axons into the tube was observed in more than half the cas es. These axons were traced from surrounding white and gray matter by anter ograde and retrograde labeling using a tetramethylrhodamine-conjugated dext ran as an intracellular marker. Control animals (n = 16) received tubes wit h inactive electrodes. It was rare to find any axons within control guidanc e channels, since adult mammalian central nervous system axons do not regen erate. This report provides evidence for not only the facilitated regeneration of adult mammalian central axons, but also their guidance, by an imposed elect ric field. (C) 1999 IBRO. Published by Elsevier Science Ltd.