Role of degenerating axon pathways in regeneration of mouse soleus motor axons.

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1. The recovery of tension in mouse soleus was assayed 1-5 days after crushing the extramuscular nerve in muscles which had been previously either denervated by nerve crush, partly denervated by spinal nerve root section, or paralysed by I.M. injection of botulinum toxin. Recovery of tension following nerve crush in contralateral control muscles from the same mice was also measured. The muscles were then stained with zinc iodide-osmium and examined in the light microscope. 2. Recovery in control muscles began at about 50 hr after crush and was nearly complete by 5 days. Recovery began at about 50 hr after crush and was nearly complete by 5 days. Recovery began about 10 hr earlier and was more rapid in muscles denervated by crushing the muscle nerve 4 days before recrushing at the same site. 3. Paralysis 12 days earlier by intramuscular injection of botulinum toxin did not enhance recovery after nerve crush. The axons remained following partial denervation 6 days before nerve crush also regenerated at a rate similar to controls. 4. It is concluded that (1) nerves regenerate more quickly down a pre-degenerated pathway, (2) chromatolysis does not significantly enhance reinnervation, and (3) each motor axon regenerating after a crush is constrained to follow its own denervated pathway back into the muscle. 5. Histology was consistent with these conclusions, and also showed that end-plates in control muscles reinnervated after short periods of denervation were normal in appearance and possessed little "escaped' nerve growth. This was in contrast to end-plates which had been regenerated in muscle after a preceding nerve crush, botulinum toxin paralysis or partial denervation. This suggests that growth from nerve terminals is controlled locally within a muscle.

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