REGENERATIVE POTENTIAL OF MUSCLE SPINDLES AFTER TRAUMA

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We plan to examine the potential of mammalian muscle spindles for restoration following skeletal muscle injury. The autografted (transplanted) rat soleus muscle is used as an experimental model of post-traumatic muscle regeneration and repair. Our aim is to explore the origin and formation of muscle spindles in the grafted muscles, and to establish the structure and patterns of innervation of regenerated spindles. An important goal is to determine whether spindles will form anew. To answer this question, we shall graft the digastric, a muscle devoid of spindles, into a site formerly occupied by a spindle-containing muscle (a site with potential for the formation of spindles). Another objective is to assess the respective roles of sensory and motor nerve fibers in determining the structure of regenerated spindles. For this reason, we shall examine spindles in muscles that have regenerated in the absence of sensory or motor innervation. Neurotrophic influences of motor axons on properties of intrafusal fibers will be separated from influences of activity by comparison of muscle spindles that have regenerated in a site devoid of motor innervation and those that have regenerated in quiescent, motor-innervated muscles to normal rat spindles. Lastly, we shall determine whether spindles in the regenerated muscle have morphological properties and motor and sensory innervation of the kind that would allow them to function in a normal manner. The study will use serial-sectioning histological and histochemical techniques, employing both light and electron microscope. Frozen tissues will be stained for enzymes which delineate types of intrafusal muscle fiber, as well as sensory and motor innervation. Muscles embedded in resin will be stained in serial sections to allow reconstructions of branching patterns of sensory and motor axons entering the spindles and examination of the form of nerve terminals. These techniques permit detailed quantitative comparison of the structure of spindles in normal and regenerated muscles. Investigation of muscle spindles in regenerating muscle grafts will contribute to the understanding of how transplanted or injured muscles are re-established as functional entities.