Regeneration of rat sciatic nerves in silicone tubes: Characterization of the response to low intensity d.c. stimulation

Abstract

Endogenous d.c. electric fields have been postulated to play a role in normal development and repair functions of a variety of living systems. The corollary hypothesis, that exogenous electric fields can alter development and repair mechanisms, has led to the use of d.c. electric fields as a means to enhance mammalian peripheral nerve regeneration. This study investigates the response of transected rat sciatic nerves within silicone tubes to low intensity d.c. stimulation. In 40 rats, the right sciatic nerves were transected and sutured into silicone tubes, leaving a 5.0 mm gap between the stumps. The nerves were either treated with 10 μA d.c., with the cathode at the midpoint of the tube and the anode distant, or received no exogenous current. Three weeks later, transverse sections from the center of the tissue bridging the two segments were analysed by sampling approximately 12% of the cross sectional area, using × 1000 magnification on the light microscope. All non-stimulated (control) nerves showed regeneration of myelinated axons at the center of the bridge, while only 35% of the nerves stimulated with 10 μA had such a response. Of the nerves with regeneration of myelinated axons at the center of the tube, the control nerves had significantly more myelinated axons ( P = 0.0028) than treated nerves. Stimulated nerves showed bizarre regeneration responses, including formation of multiloculated cysts and neuroma-like formations. In control nerves there was a gradual tapering of axon number from proximal to distal in the regeneration bridge, while in the stimulated nerves there was a sharp decrease in the number of axons proximal to the cathode. We hypothesize that this effect is due to the accumulation of electrolysis products at the cathode, which inhibit regeneration through this region. Regeneration of transected rat sciatic nerves is not enhanced by electric currents applied in this manner. Previous work interpreted the increased number of axonal cross-sections in the tube as an increase in the absolute number of regenerating fibers. Our data suggest that the increased number of axonal cross-sections is due to neuroma formation, probably in response to the accumulation of electrolysis products at the cathode. This work brings into question claims of an enhancement of peripheral nerve regeneration by applied electric fields.