The effects of ischaemia and denervation on mammalian muscle spindles

Abstract

The effects of ischaemia and denervation on rat muscle spindles have been investigated in a series of experiments in which the soleus muscle was either devascularized, or denervated, or devascularized and denervated at the same time. The structure of the experimental spindles was observed with the electron microscope at various postoperative periods. Soleus muscle is revascularized 5 days after sectioning its supplying blood vessels. The temporary ischaemia thus produced results in the rapid concomitant degeneration of both extrafusal and intrafusal muscle fibres as well as their nerve terminals and supplying axons. The basal lamina of the intrafusal fibres remains intact and necrotic debris is removed by phagocytic cells. Satellite cells survive the temporary ischaemia, giving rise to numerous myoblasts within the basal-lamina tubes. The myoblasts fuse to form myotubes, by the 14th day after devascularization, are maturing into thin muscle fibres, in the absence of any innervation. Reinnervation of the regenerating spindle begins 21 days after devascularisation and is completed some 7 days later, during which time further differentiation of reinnervated intrafusal fibres occurs. Regenerated spindles vary considerably with respect to the extent of their sensory and motor innervation and equatorial nucleation and the reasons for this variation are discussed. Most regenerated ischaemic spindles and denervated spindles contain short, thin additional muscle fibres, the sources of which are also discussed. The degeneration and regeneration of ischaemic muscle spindles are not affected by sectioning the muscle nerve at the time of devascularization. Differences are only seen at the later post- operative stages when further differentiation of the intrafusal fibres does not occur, presumably because of the absence of reinnervating axon terminals. Instead, signs of denervation atrophy are seen in non-innervated regenerated ischaemic spindles. In contrast to the rapid effects of devascularization, denervation results in a slow atrophy of intrafusal fibres. Equatorial nuclei are replaced by myofibrils. As long as one year after denervation only focal atrophy of intrafusal fibres is evident, contrasting markedly with the widespread extensive atrophy of extrafusal fibres. The significance of these results is discussed in relation to other experimental studies of the regeneration or reinnervation of muscle spindles. Their possible clinical application in nerve and muscle repair is also highlighted.