The Basis for Diminished Functional Recovery after Delayed Peripheral Nerve Repair

Gordon, Tessa; Tyreman, Neil; Raji, Mukaila

doi:10.1523/jneurosci.6156-10.2011

Cited by 281 publications

(271 citation statements)

References 62 publications

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“…Motor neurons in the spinal cord survive peripheral transection [10] due to tropic support from Schwann cells in the proximal nerve and from re-innervated muscle after chronic injury [4]. We did not observe motor deficits after delivery of a Wnt pathway inhibitor, demonstrating that loss of MN in our model was wortmannin specific and likely represents suicide transport.…”

Section: Spine Research Issn 2471-8173mentioning

confidence: 73%

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Peripheral Nerve Suicide Transport Generates a Reproducible SCI

Pagano¹,

Liang²,

Chrzan³

et al. 2017

Spine Research

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Section: Spine Research Issn 2471-8173mentioning

confidence: 73%

“…Current therapies are inadequate in current animal models of spinal cord injury (SCI) [1][2][3][4][5][6][7]. A common objective is to mimic clinical SCI by generating a chaotic wound through cord laminectomy followed by controlled impact [2].…”

mentioning

confidence: 99%

Peripheral Nerve Suicide Transport Generates a Reproducible SCI

Pagano¹,

Liang²,

Chrzan³

et al. 2017

Spine Research

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“…In fact, since prevention of muscle atrophy and degeneration is a key issue for successful func-tional recovery after nerve injury [44], it is very important that the regenerated axons reach their target as much rapidly as possible. In this view, the effects, both direct or glial cell-mediated, on neurite elongation exerted by NRG1 could represent a very positive tool on axonal regeneration after nerve injury in vivo.…”

Section: Discussionmentioning

confidence: 99%

Neuregulin1 administration increases axonal elongation in dissociated primary sensory neuron cultures

Audisio

Mantovani

Raimondo

et al. 2012

Experimental Cell Research

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Neuregulin1 is a family of growth and differentiation factors involved in various functions of both peripheral and central nervous system including the regenerative processes that underlie regeneration of damaged peripheral nerves. In the present study we tested in vitro the effect of Neuregulin1 administration on dissociated rat dorsal root ganglion (DRG). Activity of neuregulin1 was compared to the activity of nerve growth factor in the same in vitro experimental model. Results showed that neurite outgrowth is enhanced by the addition of both neuregulin1 and nerve growth factor to the culture medium. While neuregulin1 was responsible for the growth of longer neurites, DRG neurons incubated with nerve growth factor showed shorter and more branched axons. Using enzyme-linked immunosorbent assay we also showed that the release of nerve growth factor, but not of brain derived neurotrophic factor is improved in DRG neuron treated with neuregulin1. On the other hand, the assay with growth factor blocking antibody, showed that effects exerted by neuregulin1 on neurite outgrowth is only partially due to the release of nerve growth factor. Taken together the results of this study provide a better understanding on the role of neuregulin1 in sensory neurons.

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“…During these studies it was observed that the administration of FK506, at concentrations far below that required for its immunosuppressant function (5 mg/kg/day down to 0.05 mg/kg/day for 4 weeks), influenced axon regeneration. FK506 (1) induces a 2-fold increase in the number of axons that regenerate, (2) increases the speed of axon regeneration across 4 cm gaps, (3) increases the number of myelinated axons by 40% , (4) significantly increases myelin thickness, (5) increases the specificity of sensory and motor target reinnervation, and (6) increases the extent of neurological recovery [346][347][348][349][350][351][352][353][354][355][356].…”

Section: Immunosuppressantsmentioning

confidence: 99%

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

Kuffler¹

2015

Int J Neurorehabilitation Eng

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Repairing Peripheral Nerves following Traumas Nerve crushWithin several days of crushing a peripheral nerve, the injured axons begin to regenerate through their distal pathway until they reach their original targets with which they restore neurological function. The larger the number of axons that regenerate through the distal nerve, the greater the extent of neurological recovery [1][2][3]. The number of axons that regenerate, and thus neurological recovery, is influenced by the physiological state of the distal denervated nerve pathway [4][5][6][7].Following a peripheral nerve crush, the injured axons begin to regenerate within 2 days of injury [8]. They may regenerate to their targets through their original pathway in association with and promoted by its Schwann cells, the neurotrophic factors they release, and the Schwann cell extracellular matrix [1,4,[9][10][11][12][13][14]. Thus, the distal nerve provides a simple means for promoting and directing the regenerating axons to their original targets [15][16][17][18]. However, when a nerve has a gap, the gap must be bridged with a material that is permissive to and promotes axon regeneration across the entire gap to reach the distal nerve stump, through which the axons must then be able to regenerate.The Schwann cells in the denervated distal nerve release neurotrophic factors that promote axon regeneration, but also release extracellular matrix components that promote and inhibit axon regeneration [19][20][21][22][23][24][25][26]. Thus, regeneration through the distal nerve is a balance of the influences of factors that both promote and inhibit regeneration. If the Schwann cells are present, such as after a simple nerve crush, virtually 100% of the axons regenerate and they innervate all the denervated synaptic sites. If the Schwann cells within the distal nerve pathway are killed, leaving only the extracellular matrix intact, the number of axons that regenerates to their targets decreases by 94%. This is because the factors required to trigger the regenerating axons to branch at extracellular matrix branch points are missing, axons do not branch, and therefore each axon reinnervates only a single denervated muscle fiber. Thus, Schwann cells along the distal nerve pathway and a AbstractFollowing a peripheral nerve crush, or when a peripheral the nerve is transected and the nerve stumps anastomosed, neurological recovery is generally excellent. This is because the axons merely have to regenerate through the distal portion of the nerve through the existing extracellular matrix of the denervated Schwann cells that direct and promote them to their distant denervated motor and sensory targets. However, when a length of a peripheral nerve is destroyed, and anastomosis is not possible, the standard surgical repair technique is to graft a length/s of autologous sensory nerve into the gap. Neurological recovery is generally good if the nerve gap is <2 cm in length, the repair is performed <4 months post trauma, and the patients are <25 years of age. Because the nerve ...

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The Basis for Diminished Functional Recovery after Delayed Peripheral Nerve Repair

Cited by 281 publications

References 62 publications

Peripheral Nerve Suicide Transport Generates a Reproducible SCI

Peripheral Nerve Suicide Transport Generates a Reproducible SCI

Neuregulin1 administration increases axonal elongation in dissociated primary sensory neuron cultures

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

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