Reinnervation and regeneration of denervated rat skeletal muscles.

This study was undertaken as part of an effort to restore the mass and force generating ability that are lost when a skeletal muscle is denervated. It found that grafting with nerve implantation significantly improved the functional capacity of one- to 7-month denervated rat extensor digitorum longus (EDL) muscles over the denervated state. However, functional restoration was poorer in grafts of 7-month denervated muscles than in grafts of muscles denervated for shorter periods of time. Two questions regarding the functional restoration of denervated muscles emerged from these findings. The first was whether or not nerve implantation in the absence of grafting could account for the restoration of the denervated muscles. The second was whether or not there were differences between short-term and long-term denervated muscles which could account for the differences in functional restoration after grafting and nerve implantation. The first question was addressed by locally denervating rat soleus muscles for two months and then implanting their nerves with or without concomitant grafting of the muscles. Soleus muscles which were grafted with nerve implants generated twice the tetanic force of muscles which received nerve implants but were not grafted. This finding led to the hypothesis that there may be differences between the response of long-term and short-term denervated muscles to grafting which would account for the difference in the force generating ability of these muscles after they were grafted. This hypothesis was supported by the finding that muscle fibers within grafts of 7-month denervated EDL muscles degenerated and regenerated very poorly compared with fibers in muscles which were not denervated prior to grafting. The force generating ability of the denervated muscles was significantly improved when their fibers were induced to degenerate and regenerate with Marcaine treatment; Marcaine is a myotoxic anesthetic. The finding that the force generating ability of denervated muscles can be significantly restored when the muscles regenerate after they are grafted opens an exciting avenue of research into the clinical treatment of denervated muscles.PhDBiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/104744/1/9610078.pdfDescription of 9610078.pdf : Restricted to UM users only