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      Peripheral Nerve Reconstruction after Injury: A Review of Clinical and Experimental Therapies

      review-article
      * ,
      BioMed Research International
      Hindawi Publishing Corporation

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          Abstract

          Unlike other tissues in the body, peripheral nerve regeneration is slow and usually incomplete. Less than half of patients who undergo nerve repair after injury regain good to excellent motor or sensory function and current surgical techniques are similar to those described by Sunderland more than 60 years ago. Our increasing knowledge about nerve physiology and regeneration far outweighs our surgical abilities to reconstruct damaged nerves and successfully regenerate motor and sensory function. It is technically possible to reconstruct nerves at the fascicular level but not at the level of individual axons. Recent surgical options including nerve transfers demonstrate promise in improving outcomes for proximal nerve injuries and experimental molecular and bioengineering strategies are being developed to overcome biological roadblocks limiting patient recovery.

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          Most cited references85

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          Experiments on the Section of the Glossopharyngeal and Hypoglossal Nerves of the Frog, and Observations of the Alterations Produced Thereby in the Structure of Their Primitive Fibres

          A. Waller (1850)
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            A 25-year perspective of peripheral nerve surgery: evolving neuroscientific concepts and clinical significance.

            G Lundborg (2000)
            In spite of an enormous amount of new experimental laboratory data based on evolving neuroscientific concepts during the last 25 years peripheral nerve injuries still belong to the most challenging and difficult surgical reconstructive problems. Our understanding of biological mechanisms regulating posttraumatic nerve regeneration has increased substantially with respect to the role of neurotrophic and neurite-outgrowth promoting substances, but new molecular biological knowledge has so far gained very limited clinical applications. Techniques for clinical approximation of severed nerve ends have reached an optimal technical refinement and new concepts are needed to further increase the results from nerve repair. For bridging gaps in nerve continuity little has changed during the last 25 years. However, evolving principles for immunosuppression may open new perspectives regarding the use of nerve allografts, and various types of tissue engineering combined by bioartificial conduits may also be important. Posttraumatic functional reorganizations occurring in brain cortex are key phenomena explaining much of the inferior functional outcome following nerve repair, and increased knowledge regarding factors involved in brain plasticity may help to further improve the results. Implantation of microchips in the nervous system may provide a new interface between biology and technology and developing gene technology may introduce new possibilities in the manipulation of nerve degeneration and regeneration.
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              Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation.

              The effects of prolonged denervation, independent from those of prolonged axotomy, on the recovery of muscle function were examined in a nerve cross-anastomosis paradigm. The tibialis anterior muscle was denervated for various durations by cutting the common peroneal nerve before a freshly cut tibial nerve was cross-sutured to its distal stump. Nerve regeneration and muscle reinnervation were quantified by means of electrophysiological and histochemical methods. Progressively fewer axons reinnervated the muscle with prolonged denervation; for example, beyond 6 months the mean (+/- SE) motor unit number was 15 +/- 4, which was far fewer than that after immediate nerve suture (137 +/- 21). The poor regeneration after prolonged denervation is not due to inability of the long-term denervated muscle to accept reinnervation because each regenerated axon reinnervated three- to fivefold more muscle fibers than normal. Rather, it is due to progressive deterioration of the intramuscular nerve sheaths because the effects of prolonged denervation were simulated by forcing regenerating axons to grow outside the sheaths. Fewer regenerated axons account for reinnervation of less than 50% of the muscle fibers in each muscle and contribute to the progressive decline in muscle force. Reinnervated muscle fibers failed to fully recover from denervation atrophy: muscle fiber cross-sectional area being 1171 +/- 84 microns2 as compared to 2700 +/- 47 microns2 after immediate nerve suture. Thus, the primary cause of the poor recovery after long-term denervation is a profound reduction in the number of axons that successfully regenerate through the deteriorating intramuscular nerve sheaths. Muscle force capacity is further compromised by the incomplete recovery of muscle fibers from denervation atrophy.
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                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2014
                3 September 2014
                : 2014
                : 698256
                Affiliations
                Plastic and Reconstructive Surgery Unit, St. Vincent's Hospital, 41 Victoria Parade, Fitzroy, Melbourne, VIC 3065, Australia
                Author notes

                Academic Editor: Mario I. Romero-Ortega

                Article
                10.1155/2014/698256
                4167952
                25276813
                9b83ffb9-a939-4fca-b393-2a3943dd68ed
                Copyright © 2014 D. Grinsell and C. P. Keating.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 February 2014
                : 16 June 2014
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                Review Article

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