Modification of retrograde degeneration in transected spinal axons of the lamprey by applied DC current

Abstract

In the spinal cord of the lamprey, regeneration of giant reticulospinal axons occurs following transection. We show that partial degeneration of the proximal axonal segment, or "die-back," also occurs following spinal transection and it precedes regenerative outgrowth. The die-back during the first 5 days post-transection is reduced significantly by application of a 10-microA DC current across the site of transection, with the cathode distal to the lesion. Reversing the polarity of the applied current (cathode proximal to the lesion) increases the extent of axonal die-back relative to the sham-treated controls. Following spinal transection, saline-filled wick electrodes were implanted in the body musculature on either side of the lesion. Electrically treated animals received current across the lesion for 5 days, while the sham-treated controls received no current. After 5 days, several giant axons in each preparation were injected intracellularly in the spinal cord with the dye Lucifer Yellow. The extent of axonal die-back in the proximal cord stump was determined in the filled fibers by measuring the distance of the axon end from the site of lesion. The mean distances of axonal die-back were as follows: controls, 1750 microns +/- 45 SEM; cathode-distal, 740 microns +/- 33 SEM; cathode-proximal, 2820 microns +/- 60 SEM. These differences between the treatment groups proved to be significant using the Wilcoxon rank sum test. We propose that die-back is caused by the entry of cations driven into the cut surface of the cord by the endogenous injury current. The applied DC current interacts with the endogenous current of injury to either decrease or increase the flow of cations into the cord, depending on the direction of applied current flow across the lesion. This in turn causes a corresponding reduction or enhancement of the axonal die-back.

The Effects of Electroacupuncture on Peripheral Nerve Regeneration in Rats

“…The results of these experiments indicate that peripheral nerve regeneration was accelerated by distal cathode DC application but was rather delayed by distal anode DC application and therefore, support the findings reported by Pomeranz et al, 8 and Roederer et al 20 The results obtained also indicate that electroacupuncture, which applies DC stimulation, may provide a simple and safe method of enhancing nerve regeneration in a non-invasive manner. How the cathode DC application enhances the regeneration of peripheral nerves remains to be determined, but the following two hypotheses have been presented.…”

“…24 While Wallerian degeneration usually develops at or distal to the injury site, increased Ca2+ entry into the site proximal to injury causes retrograde degeneration, leading to the so-called 'die-back' phenomenon. 20 In an experiment using lamprey axons, it was confirmed that the 'die-back' phenomenon was suppressed by cathode DC application to the site distal to the injury but was enhanced by the same treatment applied to the site proximal to the injury. 20 The enhancement of axonal regeneration by distal cathode DC application in contrast to its delay by distal anode DC application via an acupuncture needle observed in the present study might have both or either of the two mechanisms mentioned above.…”

Conditioning lesions enhance axonal regeneration of descending brain neurons in spinal‐cord‐transected larval lamprey

“…Thus, in the present study, CLs at 30% BL and 50% BL transected the axons of approximately similar numbers of descending brain neurons. Second, in larval sea lamprey (80 -100 mm), injection of dye in Müller axons following spinal cord transections at ~30% BL indicates that these injured axons retract or "die back" an average of ~1.75 mm (Roederer et al, 1983). Similar results have been obtained with serial sections of the spinal cord rostral to a transection (Rovainen, 1976).…”

Localized and Transient Elevations of Intracellular Ca2+Induce the Dedifferentiation of Axonal Segments into Growth Cones

“…After the formation of a membrane seal over the cut end , [Ca 2ϩ ] i rapidly recovers to control levels. Previous studies suggested that this calcium influx induces a gradient of ultrastructural damage or even neuronal death (Schlaepfer, 1974;Meiri et al, 1983;Roederer et al, 1983;Lucas et al, 1985;Emery et al, 1987;Gross and Higgens, 1987;Spira et al, 1993) (see also Zelena et al, 1968;Ballinger and Bittner, 1980;Gross et al, 1983;Baas and Heidemann, 1986;Krause et al, 1994). However, the relationships between the [Ca 2ϩ ] i gradient and the ultrastructural alterations have not been determined.…”