Changes in nerve fiber numbers distal to a nerve repair in the rat sciatic nerve model

Mackinnon, Susan E.; Dellon, A. Lee; O’Brien, John P.

doi:10.1002/mus.880141113

Cited by 255 publications

(172 citation statements)

References 13 publications

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“…The explanation for fiber type transition in reinnervated soleus might be either the partial denervation of certain fiber populations because of axon loss (Mackinnon et al 1991;Lloyd et al 2007) and/or the random reinnervation of muscles by axons of different motoneuron pools (Bodine-Fowler et al 1997;Gramsbergen et al 2000;Ijkema-Paassen et al 2001). In accordance with the literature (Ijkema-Paassen et al 2001), we found that the total fiber number significantly decreased in reinnervated soleus when compared with normal soleus, which suggests that at least one population of denervated fibers, delayed in reinnervation, has been eliminated.…”

Section: Discussionsupporting

confidence: 89%

Regeneration of Reinnervated Rat Soleus Muscle Is Accompanied by Fiber Transition Toward a Faster Phenotype

Mendler

Pintér

Kiricsi

et al. 2007

J Histochem Cytochem.

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S U M M A R Y The functional recovery of skeletal muscles after peripheral nerve transection and microsurgical repair is generally incomplete. Several reinnervation abnormalities have been described even after nerve reconstruction surgery. Less is known, however, about the regenerative capacity of reinnervated muscles. Previously, we detected remarkable morphological and motor endplate alterations after inducing muscle necrosis and subsequent regeneration in the reinnervated rat soleus muscle. In the present study, we comparatively analyzed the morphometric properties of different fiber populations, as well as the expression pattern of myosin heavy chain isoforms at both immunohistochemical and mRNA levels in reinnervated versus reinnervated-regenerated muscles. A dramatic slow-tofast fiber type transition was found in reinnervated soleus, and a further change toward the fast phenotype was observed in reinnervated-regenerated muscles. These findings suggest that the (fast) pattern of reinnervation plays a dominant role in the specification of fiber phenotype during regeneration, which can contribute to the long-lasting functional impairment of the reinnervated muscle. Moreover, because the fast II fibers (and selectively, a certain population of the fast IIB fibers) showed better recovery than did the slow type I fibers, the faster phenotype of the reinnervated-regenerated muscle seems to be actively maintained by selective yet undefined cues. (J Histochem Cytochem 56:111-123, 2008)

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Section: Discussionsupporting

confidence: 89%

Regeneration of Reinnervated Rat Soleus Muscle Is Accompanied by Fiber Transition Toward a Faster Phenotype

Mendler

Pintér

Kiricsi

et al. 2007

J Histochem Cytochem.

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“…Moreover, we found less regenerating neurons in the retrotracer study than MFs in the histology. Although this results could seem contradictory, it has been reported that neurons initially generate several axonal sprouts after axotomy (Mackinnon et al, 1991), and even at long term each neuron may maintain more than a single regenerated axonal branch (Gómez et al, 1996;Jenq & Coggeshall, 1985). Furthermore, more regenerated axons (sprouts) do not necessarily indicate more neurons regenerating (Piquilloud et al, 2007) and may be also considered deleterious in terms of functional recovery (Guntinas-Lichius et al, 2005).…”

Section: Discussionmentioning

confidence: 98%

Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

et al. 2016

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Neurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release different NTFs and evaluate whether they accelerate axonal regeneration in comparison with free NTFs or controls. ELISA, SEM, UV/visible light microscopy, organotypic cultures of DRG explants and spinal cord slices were used to characterize MP properties and the bioactivity of the released NTFs. Results of organotypic cultures showed that encapsulated NTFs maintain longer bioactivity and enhance neurite regeneration of both sensory and motor neurons compared with free NTFs. For in vivo assays, the rat sciatic nerve was transected and repaired with a silicone tube filled with collagen gel or collagen mixed with PBS encapsulated MPs (control groups) and with free or encapsulated NGF, BDNF, GDNF or FGF-2. After 20 days, a retrotracer was applied to the regenerated nerve to quantify motor and sensory axonal regeneration. NTF encapsulation in MPs improved regeneration of both motor and sensory axons, as evidenced by increased numbers of retrolabeled neurons. Hence, our results show that slow release of NTFs with PLGA MP enhance nerve regeneration.

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“…The effect may be that sprout terminals are overloaded with calcium and result in an overall reduction of sprouting. The end result may be to accelerate the normal process of pruning that occurs during the regeneration process (Mackinnon, et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Treadmill training promotes axon regeneration in injured peripheral nerves

Sabatier

Redmon

Schwartz

et al. 2008

Experimental Neurology

145

146

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Physical activity after spinal cord injury promotes improvements in motor function, but its effects following peripheral nerve injury are less clear. Although axons in peripheral nerves are known to regenerate better than those in the CNS, methods of accelerating regeneration are needed due to the slow overall rate of growth. Therefore we studied the effect of two weeks of treadmill locomotion on the growth of regenerating axons in peripheral nerves following injury. The common fibular nerves of thy-1-YFP-H mice, in which a subset of axons in peripheral nerves express yellow fluorescent protein (YFP), were cut and repaired with allografts from non-fluorescent littermates, and then harvested two weeks later. Mice were divided into groups of low-intensity continuous training (CT, 60 minutes), low-intensity interval training (IT; one group, 10 reps, 20 minutes total), and high-intensity IT (three groups, 2, 4, and 10 reps). One repetition consisted of two minutes of running and five minutes of rest. Sixty minutes of CT resulted in the highest exercise volume, whereas two reps of IT resulted in the lowest volume of exercise. The lengths of regenerating YFP + axons were measured in images of longitudinal optical sections of nerves. Axon profiles were significantly longer than control in all exercise groups except the low-intensity IT group. In the CT group and the high-intensity IT groups that trained with four or 10 repetitions axons were more than twice as long as unexercised controls. The number of intervals did not impact axon elongation. Axon sprouting was enhanced in IT groups but not the CT group. Thus exercise, even in very small quantities, increases axon elongation in injured peripheral nerves whereas continuous exercise resulting in higher volume (total steps) may have no net impact on axon sprouting.

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Changes in nerve fiber numbers distal to a nerve repair in the rat sciatic nerve model

Cited by 255 publications

References 13 publications

Regeneration of Reinnervated Rat Soleus Muscle Is Accompanied by Fiber Transition Toward a Faster Phenotype

Regeneration of Reinnervated Rat Soleus Muscle Is Accompanied by Fiber Transition Toward a Faster Phenotype

Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

Treadmill training promotes axon regeneration in injured peripheral nerves

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