Article

Mechanisms of Disease: What factors limit the success of peripheral nerve regeneration in humans?

Neuromuscular Division, Department of Neurology at Johns Hopkins Hospital, Baltimore, MD 21287, USA.
Nature Clinical Practice Neurology (Impact Factor: 7.64). 09/2006; 2(8):448-54. DOI: 10.1038/ncpneuro0262
Source: PubMed

ABSTRACT Functional recovery after repair of peripheral nerve injury in humans is often suboptimal. Over the past quarter of a century, there have been significant advances in human nerve repair, but most of the developments have been in the optimization of surgical techniques. Despite extensive research, there are no current therapies directed at the molecular mechanisms of nerve regeneration. Multiple interventions have been shown to improve nerve regeneration in small animal models, but have not yet translated into clinical therapies for human nerve injuries. In many rodent models, regeneration occurs over relatively short distances, so the duration of denervation is short. By contrast, in humans, nerves often have to regrow over long distances, and the distal portion of the nerve progressively loses its ability to support regeneration during this process. This can be largely attributed to atrophy of Schwann cells and loss of a Schwann cell basal lamina tube, which results in an extracellular environment that is inhibitory to nerve regeneration. To develop successful molecular therapies for nerve regeneration, we need to generate animal models that can be used to address the following issues: improving the intrinsic ability of neurons to regenerate to increase the speed of axonal outgrowth; preventing loss of basal lamina and chronic denervation changes in the denervated Schwann cells; and overcoming inhibitory cues in the extracellular matrix.

1 Follower
 · 
77 Views
  • Source
    • "Autografts are commonly used to treat peripheral nerve damage caused by accidents or diseases; however, there are several disadvantages to this approach [5] [6]. In addition, although microsurgical techniques have substantially improved, peripheral nerve repair remains one of the greatest challenges of neurosurgery [2] [4] [7] [8]. Many basic research and clinical studies have demonstrated that entubulation promotes peripheral nerve reconstruction in neurotmetic injuries with a gap, permitting reconstruction of the defect without tension at the suture and creating a favorable microenvironment at the injury site. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The treatment of peripheral nerve injuries remains one of the greatest challenges of neurosurgery, as functional recover is rarely satisfactory in these patients. Recently, biodegradable nerve guides have shown great potential for enhancing nerve regeneration. A major advantage of these nerve guides is that no foreign material remains after the device has fulfilled its task, which spares a second surgical intervention. Recently, we studied peripheral nerve regeneration using chitosan-γ-glycidoxypropyltrimethoxysilane (chitosan-GPTMS) porous hybrid membranes. In our studies, these porous membranes significantly improved nerve fiber regeneration and functional recovery in rat models of axonotmetic and neurotmetic sciatic nerve injuries. In particular, the number of regenerated myelinated nerve fibers and myelin thickness were significantly higher in rat treated with chitosan porous hybrid membranes, whether or not they were used in combination with mesenchymal stem cells isolated from the Wharton's jelly of the umbilical cord. In this review, we describe our findings on the use of chitosan-GPTMS hybrids for nerve regeneration.
    BioMed Research International 06/2014; 2014:153808. DOI:10.1155/2014/153808 · 2.71 Impact Factor
  • Source
    • "Autografts are commonly used to treat peripheral nerve damage caused by accidents or diseases; however, there are several disadvantages to this approach [5] [6]. In addition, although microsurgical techniques have substantially improved, peripheral nerve repair remains one of the greatest challenges of neurosurgery [2] [4] [7] [8]. Many basic research and clinical studies have demonstrated that entubulation promotes peripheral nerve reconstruction in neurotmetic injuries with a gap, permitting reconstruction of the defect without tension at the suture and creating a favorable microenvironment at the injury site. "
  • Source
    • "The basal lamina that remains post-injury, which surrounds the axon and the Schwann cells, acts as a conduit or tube for the regenerating axon. The damaged nerve stump distal to the injury supports regeneration by assisting regenerating sprouts to extend in the direction of the distal stump (Hoke 2006). The next step in axonal regeneration occurs when the axons enter the distal stump. "
    Peripheral Neuropathy - Advances in Diagnostic and Therapeutic Approaches, 02/2012; , ISBN: 978-953-51-0066-9
Show more

Preview

Download
3 Downloads
Available from