Jean-Claude Mira

Median nerve neurotization by peripheral nerve grafts directly implanted into the spinal cord: anatomical, behavioural and electrophysiological evidences of sensorimotor recovery.

Over the years, peripheral nerve grafts, a favorable environment to support axonal elongation, have given rise to increasing interest as a possible solution for promoting spinal cord repair. In the experiments described here, following an avulsion injury of the rat brachial plexus, the median nerve was repaired by a peripheral nerve graft (PN) inserted directly into the dorsal side of the spinal cord. Eight months later the animals were submitted to behavioral tests, electrophysiological and histological studies. Regrowth of axons from both motoneurons and ganglionic neurons was demonstrated following a single superficial dorsal implantation of a PN. Sensorimotor peripheral reinnervation allowed most of the studied animals to recover enough flexor activity for grasping. Reinnervation was achieved even without prior root avulsion suggesting that the presence of a PN is sufficient to induce sprouting in the spinal cord from axotomized and non-axotomized neurons.

Variation in nerve autograft length increases fibre misdirection and decreases pruning effectiveness. An experimental study in the rat median nerve

Abstract Objectives: In the clinical set, autologus nerve grafts are the current option for reconstruction of nerve tissue losses. The length of the nerve graft has been suggested to affect outcomes. Experiments were performed in the rat in order to test this assumption and to detect a possible mechanism to explain differences in recovery. Methods: The rat median nerve was repaired by ulnar nerve grafts of different lengths. Rats were evaluated for 12 months by behavioural assessment and histological studies, including ATPase myofibrillary histochemistry and retrograde neuronal labelling. Results: It was demonstrated that graft length interferes in behavioural functional recovery that here correlates to muscle weight recovery. Short nerve grafts recovered faster and better. Reinnervation was not specific either at the trunk level or in the muscle itself. The normal mosaic pattern of Type I muscle fibres was never restored and their number remained largely augmented. An increment in the number of motor fibres was observed after the nerve grafting in a predominantly sensory branch in all groups. This increment was more pronounced in the long graft group. In the postoperative period, about a 20% reduction in the number of misdirected motor fibres occurred in the short nerve graft group only. Conclusion: Variation in the length of nerve grafts interferes in behavioural recovery and increases motor fibres misdirection. Early recovery onset was related to a better outcome, which occurs in the short graft group.

Response to denervation of rabbit soleus and gastrocnemius muscles. Time-course study of postnatal changes in myosin isoforms, fiber types, and contractile properties

In contrast to general belief, the response of rabbit muscles to denervation is maturation to slow-like type muscles [7]. We report now an investigation by biochemical, morphological, and mechanical studies of the time course effects of muscle denervation on the slow-type soleus and fast-type gastrocnemius to help elucidate the mechanism of maturation of rabbit denervated muscles to slow-like muscles. In both muscles, denervation induced selective progressive atrophy of most fast fibers and hypertrophy of many slow fibers which displayed wide Z-lines; this was accompanied by the appearance of hybrid LC1F- and LC1E-associated slow myosins. The percentage of slow myosins increased with age similarly in the contralateral and denervated soleus. On the other hand, the percentage of slow myosins remained low in the contralateral gastrocnemius, whereas it increased to 95% in the denervated gastrocnemius; in the denervated gastrocnemius, the percentage of slow myosins reached 50% at about 35 days postnatal. At this age, the maximal shortening velocity of the denervated gastrocnemius and its twitch contraction time were already those of a slow-type muscle. This suggests that in addition to myosin, other proteins contributed to the mechanical properties of the denervated gastrocnemius. Transformation of rabbit denervated muscles to slow-like type muscles, which are associated with a lower energy requirement and higher muscle endurance than fast-type muscles, may constitute an adequate model for human neuromuscular pathology.

Localization of Myf-5, MRF4 and α cardiac actin mrnas in regenerating Xenopus skeletal muscle

Abstract We have analysed the spatial and temporal expression patterns of Myf-5, MRF4 and α cardiac actin mRNAs during muscle regeneration following cardiotoxin injury in adult Xenopus laevis using in situ hybridization. Myf-5 transcripts began to be detected in the activated satellite cells as early as the beginning of the regeneration process, then dramatically decreased in young plurinucleated myotubes. MRF4 mRNA was detected later, just before the young myotube stage, and was strongly expressed during the different stages of the maturation of myotubes. Like Myf-5, α cardiac actin mRNA began to accumulate early in activated satellite cells. These results, which contribute to an overview of the expression of the genes coding for myogenic bHLH proteins during muscle regeneration, are discussed in relation to the expression of these factors during development.

Relationship between muscle myosin isoforms and contractile features in rabbit fast-twitch denervated muscle

The effects of 8‐day‐old rabbit fast‐twitch gastrocnemius denervation on the type of myosin isoforms and on contractile features (maximum velocity V max and contraction time (CT) of the muscle were followed between 15 and 60 days postnatal. The myosin isoforms and the V max and CT values of the denervated gastrocnemius displayed large changes during this period. These changes, which led at 2 months postnatal to a muscle displaying the properties of a slow‐twitch muscle did not occur in synchrony: complete conversion to slow‐type myosin isoforms occurred only at 60 days postnatal, whereas complete conversion to slow‐twitch V max and CT values occurred as soon as 35 days postnatal. The results address a new question concerning the relationship between muscle myosin and contractile features.