The effect of peripheral nerve injury on immature motor and sensory neurons and on muscle fibres. Possible relation to the histogenesis of Werdnig-Hoffmann disease.
Sciatic nerve section in newborn rats causes loss of almost all motoneurons and of two thirds of the sensory neurons. Single motor axons may regenerate but they innervate only few muscle fibres. The nonreinnervated fibres vanish and are replaced by fat cells. The reinnervated muscle fibres are overloaded, hypertrophy, and eventually necrotize. Their satellite cells regenerate new fibres; most of them develop aneurally and then disappear. The muscles, if reinnervated at all, after 1 year consist of a mixture of hypertrophic fibres, non-innervated regenerates, and fat cells, and resemble muscle from patients with infantile spinal muscular atrophy Werdnig-Hoffmann. In immature rat muscles, restricted reinnervation and functional overload of the few innervated fibres maintain a self-enhancing process which eventually leads to the replacement of the entire muscle by fat tissue. It is suggested that Werdnig-Hoffmann disease starts during fetal life and that similar mechanisms are operative. The clinical progression would then depend on the extent of degeneration due to overload and on regeneration and reinnervation in the muscles rather than on the rate of continuous loss of anterior horn cells. Immature motoneurons in rat die when they loose contact with their target; one might therefore speculate that the primary lesion in Werdnig-Hoffmann disease is peripheral rather than central, and that lack of neuronotorophic influences causes the loss of anterior horn cells.
Schmalbruch
H
H
Institute of Neurophysiology, University of Copenhagen.
D000818:Animals; D000831:Animals, Newborn; D006801:Humans; D009046:Motor Neurons / Q000473:pathology*; D009121:Muscle Denervation; D009132:Muscles / Q000473:pathology*; D009134:Muscular Atrophy, Spinal / Q000209:etiology*; D009475:Neurons, Afferent / Q000473:pathology*; D051381:Rats; D012584:Sciatic Nerve / Q000293:injuries*; D014897:Spinal Muscular Atrophies of Childhood / Q000209:etiology* / Q000473:pathology