Sprouting capacity of lumbar motoneurons in normal and hemisected spinal cords of the rat
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Nerve sprouting to reinnervate partially denervated muscles is important in several disease and injury states. To examine the effectiveness of sprouting of active and inactive motor units (MUs) and the basis for a limit to sprouting, one of three rat lumbar spinal roots was cut under normal conditions and when the spinal cord was hemisected at T12. Muscle and MU isometric contractile forces were recorded and muscle fibres in glycogen-depleted single muscle units enumerated 23 to 380 days after surgery. Enlargement of intact MUs by sprouting was effective in compensating for up to 80% loss of innervation. For injuries that removed >70-80% of the intact MUs, muscle contractile force and weight dropped sharply. For partial denervation of <70%, all MUs increased contractile force by the same factor in both normally active muscles and muscles whose activity was reduced by T12 hemisection. Direct measurements of MU size by counting glycogen-depleted muscle fibres in physiologically and histochemically defined muscle units, provided direct evidence for a limit in MU size, whether or not the activity of the muscles was reduced by spinal cord hemisection. Analysis of spatial distribution of muscle fibres within the outer boundaries of the muscle unit demonstrated a progressive increase in fibres within the territory to the limit of sprouting when most of the muscle unit fibres were adjacent to each other. We conclude that the upper limit of MU enlargement may be explained by the reinnervation of denervated muscle fibres by axon sprouts within the spatial territory of the muscle unit, formerly distributed in a mosaic pattern.Keywords:
Sprouting
Reinnervation
Motor unit
Mammalian skeletal muscle undergoes profound atrophy after denervation. The functional restoration of denervated muscle is a significant clinical problem, and the success of restorative attempts decreases substantially after several months of denervation. Rat extensor digitorum longus muscles are capable of excellent restoration for the first 2-3 months after denervation, but after that time the level of restoration upon reinnervation decreases dramatically. Severe atrophy precedes the loss of restorative capacity. Attempts to understand the basis for the reduced restorative ability have led to an intensive analysis of the biology of long-term denervated muscle. In fast muscles, the satellite cell population undergoes a major increase over the first 2 months after denervation, and thereafter it steadily declines. Atrophying muscle fibers lose nuclei through apoptosis, and some degenerate. New muscle fibers form either alongside atrophying muscle fibers or in place of degenerated ones. The microcirculation undergoes a tenfold diminution over the first year after denervation, and over time denervated muscle is characterized by increasing amounts of interstitial collagen. Various barriers to reinnervation are discussed. Attempts to improve the restoration of long-term denervated muscle have included the stimulation of regeneration and removal of interstitial collagen. Both of these have resulted in significant improvement in the level of functional restoration. Although chronic electrical stimulation maintains an excellent degree of mass and force in a denervated muscle, grafts of such muscles undergo no better restoration than grafts of denervated muscles.
Reinnervation
Muscle Atrophy
Contractility
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Reinnervation
Muscle spindle
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Abstract A typical aspect of motoneuron plasticity is the sprouting which occurs during muscle reinnervation, resulting in a transitory multiple innervation of the muscle cells. In order to verify the effect of a decreased protection from free radical attack on the sprouting, the multiple innervation in the extensor digitorum longus muscle, following sciatic nerve crush and regeneration, was studied in vitamin E‐deficient rats. Thus, the innervated end‐plates and the end‐plates with multiple innervation were studied with histochemical and electrophysiological techniques. The percentage of innervated end‐plates was similar in both groups at 30 as well as at 60 days after nerve crush. Nevertheless, multiple innervation was found in a larger part of the muscle and it lasted longer in the deficient rats. This finding is discussed in relation to some of the major hypotheses of sprouting; it may be relevant in the treatment of some lesions of peripheral nerve.
Reinnervation
Sprouting
Extensor digitorum muscle
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Reinnervation
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Sprouting
Extensor digitorum muscle
Extensor Digitorum Communis
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Neuromuscular junctions (NMJs) are the key interface between terminal nerves and targeted muscle, which undergo degeneration during denervation periods. Denervation-related NMJs changes limits the recovery level of nerve repair strategies. Insights into mechanisms behind neuromuscular junction degeneration and regeneration, following denervation and reinnervation, are of clinical value. Developing some therapies to maintain or protect structures and functions of NMJs may contribute to a better prognosis. Here, we reviewed previous studies of NMJs focusing on the morphological, functional, and molecular changes after denervation, and if those changes can be reversed after reinnervation. Also, we reviewed about the present probable strategies that have been applied clinically or could still be studied in targeting the neuromuscular junction protection or regeneration improvement.
Reinnervation
Degeneration (medical)
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Background We have demonstrated that the native motor zone (NMZ) within a muscle is an ideal target for performing nerve-muscle-endplate band grafting (NMEG) to restore motor function of a denervated muscle. This study was designed to determine spatiotemporal alterations of the myofibers, motor endplates (MEPs), and axons in the NMZ of long-term denervated muscles for exploring if NMEG-NMZ technique would have the potential for delayed reinnervation. Methods Sternomastoid (SM) muscles of adult female Sprague-Dawley rats (n = 21) were experimentally denervated and denervation-induced changes in muscle weight, myofiber size, MEPs, and intramuscular nerve axons were evaluated histomorphometrically and immunohistochemically at the end of 3, 6, and 9 months after denervation. The values obtained from the ipsilateral normal side served as control. Results The denervated SM muscles exhibited a progressive reduction in muscle weight (38%, 31%, and 19% of the control) and fiber diameter (52%, 40%, and 28% of the control) for 3-, 6-, and 9-month denervation, respectively. The denervated MEPs were still detectable even 9 months after denervation. The mean number of the denervated MEPs was 79%, 65%, and 43% of the control in the 3-, 6-, and 9-month denervated SM, respectively. Degenerated axons in the denervated muscles became fragmented. Conclusions Persistence of MEPs in the long-term denervated SM suggests that some surgeries targeting the MEPs such as NMEG-NMZ technique should be effective for delayed reinnervation. However, more work is needed to develop strategies for preservation of muscle mass and MEPs after denervation.
Reinnervation
Motor Endplate
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Reinnervation
Peripheral nerve injury
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The present study describes reinnervation and restoration of rat skeletal muscle denervated for the duration of 3, 6 or 12 months. Denervation of extensor digitorum longus (EDL) muscle was achieved by cutting and ligating the donor rat sciatic nerve in situ. At 3, 6 and 12 months, the denervated EDL muscles were removed and transplanted into an innervated normal leg of another rat. In addition, normal (i.e., no prior denervation) muscles were transplanted as controls for comparison. The muscles were analyzed at 4 and 12 weeks after transplantation. The EDL muscle weight and myofiber size decreased with extended denervation times. After transplantation, the muscles underwent regeneration and reinnervation, and recovered as determined by an increase in muscle mass and myofiber size. The 3-month denervated muscle regenerates recovered completely, and were similar to the non-denervated normal muscle regenerates. Reinnervation, and partial recovery of muscle weight and myofiber size was observed in 6- and 12-month denervated muscle transplants. These results document that while regeneration and reinnervation does occur in denervated muscles after transplantation, the extent of recovery is related to the duration of denervation.
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The time course for functional reinnervation and development of supersensitivity to norepinephrine (NE) in the denervated rat kidney was studied using an in situ kidney preparation perfused at constant flow. Changes in perfusion pressure were measured during renal nerve stimulation (RNS, 1-10 Hz) and after administration of NE (1-50 ng, ia) up to 8 wk after unilateral renal denervation or a sham operation. During the first 2 wk after denervation, supersensitivity to NE was present, but there was no response to RNS. Between 24 and 32 days after denervation, RNS produced responses averaging 40% of control in denervated kidneys and supersensitivity to NE was still present. A fluorescence assay was used to determine that the NE concentration in kidneys 24-32 days after denervation was less than 30% of that found in control kidneys. At 8 wk, average responses to RNS in denervated kidneys were not significantly different from innervated kidneys, while supersensitivity to NE was still present. These results indicate that functional reinnervation of the renal vasculature begins to occur between 14 and 24 days after denervation, and that complete return of function may occur by 8 wk. The response to RNS during reinnervation appears to be due to a combination of regeneration of nerve fibers and denervation supersensitivity to NE.
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