Reinnervation and recovery of mouse soleus muscle after long-term denervation

Reinnervation and recovery of the mouse soleus muscle were studied 2-10 months after denervation periods of about 7 months. To maintain denervation the right sciatic nerve was frozen 14 times at 2-week intervals. Though initially intermittent muscle reinnervation occurred, contractile force of denervated muscles was reduced to less than 10% of the contralateral muscles by the fifth nerve freezing and further declined thereafter. Following reinnervation, recovery of soleus muscle force proceeded slowly to reach plateau values after 5-6 months. Tetanic muscle force reached on average 72% (range 58-86%, n = 12) of contralateral muscles after 5-10 months, (P less than 0.01, t-test for absolute values) and 87% of unoperated animals after 10 months (P less than 0.05, n = 5). Muscle fibre diameters were significantly reduced in reinnervated muscles, but frequency distributions were normal and similarly shaped in reinnervated and control muscles, suggesting complete muscle reinnervation and the absence of denervated fibres even at 2 months of reinnervation. Total numbers of muscle fibres were similar in reinnervated (842 +/- 73 S.D., n = 15), contralateral (854 +/- 104 S.D., n = 15) and control soleus muscles (853 +/- 77 S.D., n = 5). The number of myelinated axons in regenerating soleus nerves reached control values by 3 months after the last freezing, continued to increase till 6 months (150% of control), and declined thereafter (125% at 9-10 months). In the contralateral soleus nerves the number of myelinated axons remained constant during this period. Nerve fibre diameters remained abnormally small; even after 10 months of reinnervation fibre diameters were unimodally distributed with a mean diameter of 3.3 microns in contrast to the bimodal distribution in intact nerves (mean values 3.9 and 9.0 microns, respectively). Total fibre cross-section area per nerve increased with time but reached only 54% +/- 6 S.D., (n = 3) of contralateral nerves by 10 months. The relative thickness of the myelin sheath (g-ratio) returned to normal after 9-10 months. Anatomically, muscle reinnervation appeared to be complete by 7-8 weeks since unusually small muscle fibre profiles were absent.(ABSTRACT TRUNCATED AT 400 WORDS)