Progressive denervation of skeletal muscle induced by spinal irradiation in rats

J. D. Fewings, J. B. Harris, M. A. Johnson, W. G. Bradley

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The delayed neuromuscular effects of the administration of 3500 rads of X irradiation to the lumbosacral spinal cord and cauda equina of the rat are described. The effects were compared with those of similar irradiation directed at the thoracic cord or the cauda equina. The extensor digitorum longus and soleus muscles were studied by electrophysiology, histology and histochemistry. The purpose was to examine the changes brought about in the muscles by chronic progressive denervation, and to compare these with the changes which are generally considered to be characteristic of 'primary myopathy'. Clinically normal rats of the lumbar series studied 30 days after irradiation showed muscle fiber atrophy without electrophysiologic abnormalities. The muscle fibers of similar unaffected rats studied 54 to 95 days after irradiation had a significantly lowered resting membrane potential, and showed atrophy. Muscle fibers of clinically affected rats of the lumbar series, studied 83 to 124 days after irradiation, had a reduced resting membrane potential, a reduced maximum rate of rise and a reduced overshoot of the action potential. Nearly half of the fibers had tetrodotoxin resistant action potentials, often with miniature end plate potentials indicating functional denervation. Clinically affected rats studied 130 or more days after irradiation showed similar electrophysiologic changes, though the frequent loss of the ability of motor nerve stimulation to elicit muscle fiber action potentials indicated extensive structural denervation. The histochemical studies of the extensor digitorum longus (EDL) and soleus muscles of clinically affected rats showed significant fiber atrophy and fiber type dedifferentiation without reinnervation. The evidence suggests that in rats becoming paraplegic 150 days after irradiation, functional impairment of the alpha motoneuron may have been present for at least 120 days, and that progressive denervation, initially functional and later structural, may have been occurring in the EDL and soleus muscles for at least 50 days. The histological changes in these muscles in chronic progressive denervation included disseminated single fiber atrophy, generalized or grouped muscle fiber atrophy, increased endomysial connective tissue, an increased proportion of muscle nuclei and hypertrophy and splitting of muscle fibers. It is concluded that all these changes are not diagnostic of a primary myopathy and may be seen frequently in chronic denervation of muscle. Muscle fiber necrosis, phagocytosis, and regeneration were extremely rare and do not result from the neuronal dysfunction produced by irradiation.

Original languageEnglish (US)
Pages (from-to)157-183
Number of pages27
JournalBrain
Volume100
Issue number1
DOIs
StatePublished - Dec 1 1977
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology

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