Axonal regeneration from injured dorsal roots into the spinal cord of adult rats

Chong, M.S.; Woolf, C. J.; Haque, N.S.K.; Anderson, Patrick N.

doi:10.1002/(sici)1096-9861(19990719)410:1<42::aid-cne5>3.3.co;2-6

Cited by 17 publications

(21 citation statements)

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“…Thus, exogenous treatments that boost RAG expression in these neurons also increase the number of regeneration-competent cells. Thirdly, when dorsal root ganglion (DRG) neurons are conditioned by a peripheral nerve transection, a lesion which induces RAG expression, their central axons show an enhanced regenerative response that can result in significant sprouting into the spinal cord, even beyond the lesion site (Richardson and Issa, 1984; Chong et al, 1999; Neumann and Woolf, 1999). Finally, this conditioning lesion effect was shown to be transcription dependent (Smith and Skene, 1997).…”

Section: Regeneration-associated Genes: a Historical Perspectivementioning

confidence: 99%

A Gene Network Perspective on Axonal Regeneration

Kesteren¹,

Mason²,

MacGillavry³

et al. 2011

Front. Mol. Neurosci.

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The regenerative capacity of injured neurons in the central nervous system is limited due to the absence of a robust neuron-intrinsic injury-induced gene response that supports axon regeneration. In peripheral neurons axotomy induces a large cohort of regeneration-associated genes (RAGs). The forced expression of some of these RAGs in injured neurons has some beneficial effect on axon regeneration, but the reported effects are rather small. Transcription factors (TFs) provide a promising class of RAGs. TFs are hubs in the regeneration-associated gene network, and potentially control the coordinate expression of many RAGs simultaneously. Here we discuss the use of combined experimental and computational methods to identify novel regeneration-associated TFs with a key role in initiating and maintaining the RAG-response in injured neurons. We propose that a relatively small number of hub TFs with multiple functional connections in the RAG network might provide attractive new targets for gene-based and/or pharmacological approaches to promote axon regeneration in the central nervous system.

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Section: Regeneration-associated Genes: a Historical Perspectivementioning

confidence: 99%

A Gene Network Perspective on Axonal Regeneration

Kesteren¹,

Mason²,

MacGillavry³

et al. 2011

Front. Mol. Neurosci.

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“…This is another way of inhibition than what currently is the concept (He and Koprivica, 2006). There are a number of reports of induced regeneration of dorsal roots by transplantation of glia cells (Kliot et al, 1990), conditioning lesions (Chong et al, 1999), or application of growth factors (Ramer et al, 2002; Wang et al, 2008). None of those strategies have, however, been useful for clinical applications.…”

Section: Present and Pastmentioning

confidence: 99%

Perspectives on the treatment of the longitudinal spinal cord injury

Carlstedt¹

2010

Front. Neur.

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The current technique for surgical treatment of the longitudinal spinal cord injury has proven to be successful for restoration of some motor function and alleviation of pain. This has been the first step in finding a cure for spinal cord injuries, but so far there are many obstacles still to be overcome. In this particular injury return of function from spinal cord surgery is only partial. Some of the main remaining problems are related to injury-induced neuronal death, direction and specificity of regeneration and muscle, and receptor disintegration from long time denervation. Currently this is a surgical procedure without any adjuvant treatments. In order to gain further functional improvement combinational therapies developed in basic science experiments are essential.

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“…However, a lesion inflicted on the central branch extending into the dorsal column of the spinal cord would result in a contrasting failure of regeneration. Secondly, it has been shown that regeneration of the CNS branch of these neurons could be greatly enhanced by a prior injury to the peripheral branch – the effect of a conditioning lesion (Chong et al . 1999; Neumann and Woolf 1999).…”

Section: Cyclic Amp and Crebmentioning

confidence: 99%

Axonal regeneration in adult CNS neurons – signaling molecules and pathways

Teng

Tang

2006

Journal of Neurochemistry

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Failure of severed adult CNS axons to regenerate could be attributed to both a reduced intrinsic capacity to grow and an heightened susceptibility to inhibitory factors of the CNS extracellular environment. A particularly interesting and useful paradigm for investigating CNS axonal regeneration is its enhancement at the CNS branch of dorsal root ganglion (DRG) neurons after conditional lesioning of their peripheral branch. Recent reports have implicated the involvement of two well-known signaling pathways utilizing separate transcription factors; the Cyclic AMP (cAMP) response element binding protein (CREB) and signal transducer and activator of transcription 3 (STAT3), in conditional lesioning. The former appears to be the pathway activated by neurotrophic factors and Bcl-2, while the latter is responsible for the neurogenic effect of cytokines [such as the leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) elevated at lesion sites]. Recent findings also augmented earlier notions that modulations of the activity of another class of cellular signaling intermediate, the conventional protein kinase C (PKC), could result in a contrasting growth response by CNS neurons to myelin-associated inhibitors. We discuss these signaling pathways and mechanisms, in conjunction with other recent reports of regeneration enhancement and also within the context of what is known about aiding regeneration of injured CNS axons. That axons of the adult CNS regenerate poorly after injury is the underlying reason for the devastation associated with physical or ischemic injuries to the brain and spinal cord. Other than the presence of CNS growth inhibitors (Filbin 2003;Sandvig et al. 2004), this poor regenerative capacity may be attributed to a lack of access to neurotrophic factors in the adult CNS. However, exogenous supplementation of injured CNS neurons with neurotrophins, with some exceptions (Ramer et al. 2000), had largely resulted in a limited enhancement of regeneration. Adult CNS neurons are known to be intrinsically poor in regeneration compared to the same neurons at an embryonic stage of development. Embryonic neurons are not simply more vigorous in terms of neurite outgrowth, but also more responsive to neurotrophic stimuli and most importantly, react differently to myelin-associated inhibitors. All these phenomena are readily observed in models of CNS neuron regeneration such as neurons of the dorsal root ganglia (DRG), cerebellar neurons and retinal ganglion cells (RGCs).Below, recent updates to the myriad of molecules, signaling pathways and signaling mechanisms involved in CNS axonal regeneration shall be discussed. It should be kept in mind that signaling events and processes in the regeneration of post-mitotic neurons represent a counterbalance and integration of intrinsic growth ability of the injured neuron (aided or enhanced by signals coming from various neurotrophic factors) and growth inhibitory signals from the CNS environment (such as those from the myelin-associated inhibitors). Much of the ne...

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Axonal regeneration from injured dorsal roots into the spinal cord of adult rats

Cited by 17 publications

References 0 publications

A Gene Network Perspective on Axonal Regeneration

A Gene Network Perspective on Axonal Regeneration

Perspectives on the treatment of the longitudinal spinal cord injury

Axonal regeneration in adult CNS neurons – signaling molecules and pathways

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