Tropism in nerve regeneration in vivo. Attraction of regenerating axons by diffusible factors derived from cells in distal nerve stumps of transected peripheral nerves

Politis, Michael J.; Ederle, K; Spencer, Peter S.

doi:10.1016/0006-8993(82)90667-9

Cited by 329 publications

(118 citation statements)

References 13 publications

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“…Comparing the results of a vessel-containing tube with a 25 mm gap with a 10 mm gap in a similar tube [6], the number and mean diameter of axons in the 25 mm gap were 1500 and 1.9 mm at 24 weeks compared with 8000 and 2.4 mm in the 10 mm gap. This is due to the decrease of neurotropism from the distal nerve stumps which decreases as the distance between the stumps increases [10,19,21,24]. Neurotropism is weaker in tubes with a 25 mm gap than in those with a 10 mm gap.…”

Section: Discussionmentioning

confidence: 99%

Nerve regeneration over a 25 mm gap in rat sciatic nerves using tubes containing blood vessels: the possibility of clinical application

Kakinoki

Nishijima

Ueba

et al. 1997

International Orthopaedics

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Section: Discussionmentioning

confidence: 99%

Nerve regeneration over a 25 mm gap in rat sciatic nerves using tubes containing blood vessels: the possibility of clinical application

Kakinoki

Nishijima

Ueba

et al. 1997

International Orthopaedics

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“…Also of historical interest are the experiments on the attractive effect of the distal stump (neurotropism), in which Y-shaped tubes were used with different types of tissue in the distal forks. Based on these experiments, the theory of neurotropism was first rejected by Weiss and Taylor, 68 but later the experiment was repeated by others, 1,5,8,39,50 and since then this theory has been generally accepted. In this review we will not discuss the results of these experiments in detail.…”

Section: Methods To Investigate Accuracy Of Regenerationmentioning

confidence: 99%

Misdirection and guidance of regenerating axons after experimental nerve injury and repair

Ruiter

Spinner

Verhaagen

et al. 2014

JNS

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Misdirection of regenerating axons is one of the factors that can explain the limited results often found after nerve injury and repair. In the repair of mixed nerves innervating different distal targets (skin and muscle), misdirection may, for example, lead to motor axons projecting toward skin, and vice versa-that is, sensory axons projecting toward muscle. In the repair of motor nerves innervating different distal targets, misdirection may result in reinnervation of the wrong target muscle, which might function antagonistically. In sensory nerve repair, misdirection might give an increased perceptual territory. After median nerve repair, for example, this might lead to a dysfunctional hand.Different factors may be involved in the misdirection of regenerating axons, and there may be various mechanisms that can later correct for misdirection. In this review the authors discuss these different factors and mechanisms that act along the pathway of the regenerating axon. The authors review recently developed evaluation methods that can be used to investigate the accuracy of regeneration after nerve injury and repair (including the use of transgenic fluorescent mice, retrograde tracing techniques, and motion analysis). In addition, the authors discuss new strategies that can improve in vivo guidance of regenerating axons (including physical guidance with multichannel nerve tubes and biological guidance accomplished using gene therapy). 493Abbreviations used in this paper: BDNF = brain-derived neurotrophic factor; DY = diamidino yellow; FB = fast blue; GC = growth cone; GDNF = glial cell line-derived neurotrophic factor; LV = lentiviral vector; NGF = nerve growth factor.

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“…In addition, tubularization serves to significantly reduce excessive collagen and scar formation, and prevent axons from escaping into surrounding tissues [56,[194][195][196]. Finally, conduits allow Schwann cells to migrate into the nerve gap from the distal stump and together with the in-growing axons [57,58,197,198].…”

Section: Non-biological Conduits To Bridge Nerve Gapsmentioning

confidence: 99%

“…During days 3-7 the fluid is replaced by an acellular fibronectin positive, laminin negative fibrous matrix, which is critical for Schwann cell proliferation and for Schwann cells to migrate into the tube [57,58,196,205,206]. Fibroblasts and Schwann cells migrate from both nerve stumps within 2 weeks of implantation [144,[207][208][209].…”

Section: Empty Nerve Tubesmentioning

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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Tropism in nerve regeneration in vivo. Attraction of regenerating axons by diffusible factors derived from cells in distal nerve stumps of transected peripheral nerves

Cited by 329 publications

References 13 publications

Nerve regeneration over a 25 mm gap in rat sciatic nerves using tubes containing blood vessels: the possibility of clinical application

Nerve regeneration over a 25 mm gap in rat sciatic nerves using tubes containing blood vessels: the possibility of clinical application

Misdirection and guidance of regenerating axons after experimental nerve injury and repair

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

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