Myelin sheath remodelling in regenerated rat sciatic nerve.
Adult rat sciatic nerves were subjected to a crush lesion and allowed to survive during 2 weeks-11 months. Segments of regenerated nerve were removed from exsanguinated animals and subjected to physiological analysis and light microscopic examination of teased fibres. Application of the potassium channel blocking agent 4-aminopyridine (4-AP) to regenerated nerve segments had marked effects on action potential waveform and recovery properties. When applied to normal control nerves 4-AP had minimal effects. Examination of teased preparations from the same nerves revealed the presence of two classes of internodes along regenerated nerve fibres. A majority of conventional regenerated internodes exhibited lengths (L) of at least 150 microns. Maximal L reached about 350 microns after one month survival and 550 microns 10 months later. In the individual nerve the maximal L-values tended to increase with fibre size. Most convential regenerated internodes had L-values of 200-400 microns. In addition, scattered unusually short sheaths, with L-values of 10-150 microns, were found intercalated between conventional internodes. Some intercalated sheaths had a wrinkled irregular configuration and some lacked a light-microscopically distinct myelin layer. We suggest that the occurrence of unusually short and partly distorted sheaths along regenerated fibres reflects a nodal-internodal remodelling in response to longitudinal crowding. These sites might represent foci with aberrant functional properties, possibly accounting for the 4-AP sensitivity of regenerated nerve.
Hildebrand
C
C
Kocsis
J D
JD
Berglund
S
S
Waxman
S G
SG
D015761:4-Aminopyridine; D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D005260:Female; D007473:Ion Channels / Q000502:physiology; D008297:Male; D009186:Myelin Sheath / Q000502:physiology*; D009416:Nerve Regeneration; D010525:Peripheral Nerves / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D011901:Ranvier's Nodes / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000502:physiology
D000631:Aminopyridines; D007473:Ion Channels; D015761:4-Aminopyridine; D011188:Potassium