The Rate of Regeneration of Nerve

Gutmann, E; Guttmann, Ludwig; Medawar, P. B.; Young, J. Z.

doi:10.1093/oxfordjournals.bmb.a070228

Cited by 94 publications

(132 citation statements)

References 3 publications

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“…Pinching the hindlimb digits and footpad without eliciting a foot withdrawal and vocalization was noted as loss of sensory and motor f unction (Devor and Govrin-Lippmann, 1979;Navarro et al, 1994;Verdú and Navarro, 1997). The absence of the toe spreading reflex and lateral leg extension when the mouse was gently lifted by the tail (Gutmann et al, 1942;Azzouz et al, 1996) and total lack of hindlimb movement while ambulating also indicated loss of sensory and motor f unction. Disruption of axonal integrity after crush was also confirmed by immunostaining sciatic nerve tissue sections taken proximal and distal to the crush site, with mouse anti-neurofilament (N FP) antibody.…”

Section: Methodsmentioning

confidence: 99%

Induction of the Plasminogen Activator System Accompanies Peripheral Nerve Regeneration after Sciatic Nerve Crush

Siconolfi

Seeds

2001

J. Neurosci.

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Peripheral nerve regeneration is dependent on the ability of regenerating neurites to migrate through cellular debris and altered extracellular matrix at the injury site, grow along the residual distal nerve sheath conduit, and reinnervate synaptic targets. In cell culture, growth cones of regenerating axons secrete proteases, specifically plasminogen activators (PAs), which are believed to facilitate growth cone movement by digesting extracellular matrices and cell adhesions. In this study, the PA system was shown to be specifically activated in sensory neurons after sciatic nerve crush in adult mice. The number of sensory neurons expressing urokinase PA receptor (uPAR) mRNA levels increased above sham levels by 8 hr after crush, whereas the number of sensory neurons expressing uPA and tissue PA (tPA) mRNAs was significantly increased by 3 d after crush. PA mRNA levels were also increased at the crush site, with uPA mRNA elevated by 8 hr after crush and tPA and uPAR mRNA levels markedly increased by 7 d. PA-dependent enzymatic activity was significantly increased from 1 to 7 d after crush in nerves that had been crushed compared with uncrushed nerves. Immunohistochemistry showed that tPA was localized within regenerating axons of the sciatic nerve. There were no significant changes in plasminogen activator inhibitor 1 activity between crush and sham after the injury. These results clearly demonstrated that after injury the PA system was rapidly induced in sensory neurons, where it may play an important role in nerve regeneration in vivo.

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Section: Methodsmentioning

confidence: 99%

Induction of the Plasminogen Activator System Accompanies Peripheral Nerve Regeneration after Sciatic Nerve Crush

Siconolfi

Seeds

2001

J. Neurosci.

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“…The latent period of nerve regeneration was determined by extrapolation of the regression line of the distance of nerve regeneration against the days after the nerve injury [50]. Periods of as short as a day or as long as 3 days were described with axons regenerating thereafter at rates of 1-3 mm/day in humans and rats, respectively [50][51][52][53][54][55].…”

Section: Brief Electrical Stimulation Accelerates Axon Outgrowth Acromentioning

confidence: 99%

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

2016

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Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is so particularly when injuries require regeneration over long distances and/or over long time periods. Fat replacement of chronically denervated muscles, a commonly accepted explanation, does not account for poor functional recovery. Rather, the basis for the poor nerve regeneration is the transient expression of growth-associated genes that accounts for declining regenerative capacity of neurons and the regenerative support of Schwann cells over time. Brief low-frequency electrical stimulation accelerates motor and sensory axon outgrowth across injury sites that, even after delayed surgical repair of injured nerves in animal models and patients, enhances nerve regeneration and target reinnervation. The stimulation elevates neuronal cyclic adenosine monophosphate and, in turn, the expression of neurotrophic factors and other growth-associated genes, including cytoskeletal proteins. Electrical stimulation of denervated muscles immediately after nerve transection and surgical repair also accelerates muscle reinnervation but, at this time, how the daily requirement of long-duration electrical pulses can be delivered to muscles remains a practical issue prior to translation to patients. Finally, the technique of inserting autologous nerve grafts that bridge between a donor nerve and an adjacent recipient denervated nerve stump significantly improves nerve regeneration after delayed nerve repair, the donor nerves sustaining the capacity of the denervated Schwann cells to support nerve regeneration. These reviewed methods to promote nerve regeneration and, in turn, to enhance functional recovery after nerve injury and surgical repair are sufficiently promising for early translation to the clinic.

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“…First, regeneration in the week after a crush injury was quantified by using the ''sensory pinch test.'' In this test, the distance from the nerve crush site to the foremost regenerating sensory axons is determined by pinching consecutive segments of the nerve in a distal to proximal direction until a contraction of the abdominal muscles in the back is observed (15). This test depends on retrograde conduction along sensory neurons and is independent of sciatic nerve motor function.…”

Section: Axonal Outgrowth and Regeneration Are Reduced In Drg Sensorymentioning

confidence: 99%

Targeted disruption of the galanin gene reduces the number of sensory neurons and their regenerative capacity

Holmes

Mahoney²,

King³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

193

171

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The neuropeptide galanin is expressed developmentally in the dorsal root ganglion (DRG) and is rapidly up-regulated 120-fold after peripheral nerve section in the adult. Here we report that adult mice carrying a loss-of-function mutation in the galanin gene have a 13% reduction in the number of cells in the DRG associated with a 24% decrease in the percentage of neurons that express substance P. These deficits are associated with a 2.8-and 2.6-fold increase in the number of apoptotic cells in the DRG at postnatal days 3 and 4, respectively. After crush injury to the sciatic nerve, the rate of peripheral nerve regeneration is reduced by 35% with associated long-term functional deficits. Cultured DRG neurons from adult mutant mice demonstrate similar deficits in neurite number and length. These results identify a critical role for galanin in the development and regeneration of sensory neurons. D amage to a peripheral nerve causes changes within the cell body that promote neuronal survival, axonal regeneration, and functional recovery. Under favorable conditions, for instance after a crush injury, most nerve fibers successfully regenerate. However, in many clinically relevant circumstances, traumatic or disease-induced nerve injury has a poor outcome with only limited return of function and often with considerable delay. The molecular and cellular interactions that control the degree and rate of peripheral nerve regeneration are poorly understood and remain important clinical and scientific issues.In an attempt to define the mechanisms that regulate neuronal survival and regeneration, we and others have used the approach of studying factors whose expression patterns are known to change in response to injury. One of the most potent changes in the dorsal root ganglion (DRG) after peripheral nerve injury is the 120-fold increase in the levels of the 29-aa neuropeptide galanin (1). Studies have demonstrated that galanin is expressed at high levels in most cells of the developing DRG from day 16 of gestation until shortly after birth (2). In the adult, galanin is expressed at low levels in only 2-3% of DRG cells, which are predominantly small fiber neurons (1). After axotomy, mRNA and peptide are abundantly expressed in 40-50% of all DRG neurons (3) and remain elevated while the nerve is regenerating (1). Similarly, axotomy also up-regulates galanin expression in motor (4) and sympathetic (5) neurons. The rise in expression in the dorsal horn after axotomy is modest compared with the marked elevation in the DRG (6), reflecting an increase in anterograde transport of galanin from the cell body to the site of injury (7), analogous to that described in axotomized sympathetic neurons (8). Despite these findings, there is no direct evidence that galanin plays a role in axonal regeneration after injury.We previously have generated mice carrying a loss-of-function mutation in the galanin gene (9) and most recently have demonstrated that the chronic absence of galanin throughout prenatal and postnatal development causes an atte...

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The Rate of Regeneration of Nerve

Cited by 94 publications

References 3 publications

Induction of the Plasminogen Activator System Accompanies Peripheral Nerve Regeneration after Sciatic Nerve Crush

Induction of the Plasminogen Activator System Accompanies Peripheral Nerve Regeneration after Sciatic Nerve Crush

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

Targeted disruption of the galanin gene reduces the number of sensory neurons and their regenerative capacity

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