The making of successful axonal regeneration: Genes, molecules and signal transduction pathways

Raivich, Gennadij; Makwana, Milan

doi:10.1016/j.brainresrev.2006.09.005

Cited by 154 publications

(124 citation statements)

References 289 publications

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“…The positive injury signal for IA-MN synaptic enhancement exists within an extensive and growing list of cellular and molecular changes elicited by nerve injury from neural and non-neural cells (e.g., Schwann cells and macrophages) to cause posttranslational modification and/or synthesis of axonal proteins (Ji and Strichartz, 2004;Jimenez et al, 2005;Navarro et al, 2007;Raivich and Makwana, 2007). Examination of potential signaling mechanisms underlying neural responses to injury has focused on neurotrophins and cytokines (Huang and Reichardt, 2003;Raivich and Makwana, 2007;Viviani et al, 2007).…”

Section: Signals Initiating Synaptic Enhancementmentioning

confidence: 99%

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Enhanced Transmission at a Spinal Synapse TriggeredIn Vivoby an Injury Signal Independent of Altered Synaptic Activity

Bichler¹,

Nakanishi²,

Wang³

et al. 2007

J. Neurosci.

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Peripheral nerve crush initiates a robust increase in transmission strength at spinal synapses made by axotomized group IA primary sensory neurons. To study the injury signal that initiates synaptic enhancement in vivo, we designed experiments to manipulate the enlargement of EPSPs produced in spinal motoneurons (MNs) by IA afferents 3 d after nerve crush in anesthetized adult rats. If nerve crush initiates IA EPSP enlargement as proposed by reducing impulse-evoked transmission in crushed IA afferents, then restoring synaptic activity should eliminate enlargement. Daily electrical stimulation of the nerve proximal to the crush site did, in fact, eliminate enlargement but was, surprisingly, just as effective when the action potentials evoked in crushed afferents were prevented from propagating into the spinal cord. Consistent with its independence from altered synaptic activity, we found that IA EPSP enlargement was also eliminated by colchicine blockade of axon transport in the crushed nerve. Together with the observation that colchicine treatment of intact nerves had no short-term effect on IA EPSPs, we conclude that enhancement of IA-MN transmission is initiated by some yet to be identified positive injury signal generated independent of altered synaptic activity. The results establish a new set of criteria that constrain candidate signaling molecules in vivo to ones that develop quickly at the peripheral injury site, move centrally by axon transport, and initiate enhanced transmission at the central synapses of crushed primary sensory afferents through a mechanism that can be modulated by action potential activity restricted to the axons of crushed afferents.

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Section: Signals Initiating Synaptic Enhancementmentioning

confidence: 99%

“…Examination of potential signaling mechanisms underlying neural responses to injury has focused on neurotrophins and cytokines (Huang and Reichardt, 2003;Raivich and Makwana, 2007;Viviani et al, 2007). These and other can- Values are mean of means from individual rats Ϯ SEM.…”

Section: Signals Initiating Synaptic Enhancementmentioning

confidence: 99%

Enhanced Transmission at a Spinal Synapse TriggeredIn Vivoby an Injury Signal Independent of Altered Synaptic Activity

Bichler¹,

Nakanishi²,

Wang³

et al. 2007

J. Neurosci.

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“…The transcription factor, nuclear factor kappa B (NFĸB), bears a specific code, which is called a nuclear localization sequence, and allows the entrance in the nucleus. Trauma to the nerve may inactivate this factor and thereby it also is an important negative modulator of the response in the nerve cell body (Raivich & Makwana, 2007). After transection, the proximal tip of the axon is rapidly sealed after extracellular cations, such as Na + and Ca 2+ , are diffused through the open cell membrane.…”

Section: The Intrinsic Response In Neurons and Schwann Cells After Inmentioning

confidence: 99%

“…The entrance of calcium is also reported to be important for local activation of protein kinases at the tip of the axons. One example of such a locally activated protein kinases is extracellular signal-regulated kinase (ERK) that is fundamental for activation both in neurons and in Schwann cells (Mårtensson, Gustavsson, Dahlin, & Kanje, 2007;Raivich & Makwana, 2007;Stenberg, Kanje, Martensson, & Dahlin, 2011). The microenvironment also contains molecules that are produced by the Schwann cells, from invading inflammatory cells as well as from other injured axons.…”

Section: The Intrinsic Response In Neurons and Schwann Cells After Inmentioning

confidence: 99%

“…Thus, a substantial number of different molecules are activated by different mechanisms in neurons after injury. They are all of importance for the survival of neurons and particularly for redirection to the production of substances needed for nerve regeneration (Abe & Cavalli, 2008;Raivich & Makwana, 2007;Rossi, Gianola, & Corvetti, 2007).…”

Section: The Intrinsic Response In Neurons and Schwann Cells After Inmentioning

confidence: 99%

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The Role of Timing in Nerve Reconstruction

Dahlin

2013

International Review of Neurobiology

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The surgeon, who treats nerve injuries, should have knowledge about how peripheral nerves react to trauma, particularly an understanding about the extensive pathophysiological alterations that occur both in the peripheral and in the central nervous system. A large number of factors influence the functional outcome, where the surgeon only can affect a few of them.In view of the new knowledge about the delicate intracellular signaling pathways that are rapidly initiated in neurons and in non-neuronal cells with the purpose to induce nerve regeneration, the timing of nerve repair and reconstruction after injury has gained more interest. It is crucial to understand and to utilize the inborn mechanisms for survival and regeneration of neurons and for activation, survival and proliferation of the Schwann cells and other cells that are acting after a nerve injury. Thus, experimental and clinical data clearly point towards the advantage of early nerve repair and reconstruction of injuries. Following an appropriate diagnosis of a nerve injury, the nerve should be promptly repaired or reconstructed, and new rehabilitation strategies should early be initiated. Considering nerve transfers in the treatment arsenal can shorten the time of nerve reinnervation of muscle targets. Timing of nerve repair and reconstruction is crucial after nerve injury.

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Repairing Peripheral Nerves: Is there a Role for Carbon Nanotubes?

Oprych

Whitby

Mikhalovsky

et al. 2016

Adv Healthcare Materials

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Peripheral nerve injury continues to be a major global health problem that can result in debilitating neurological deficits and neuropathic pain. Current state‐of‐the‐art treatment involves reforming the damaged nerve pathway using a nerve autograft. Engineered nerve repair conduits can provide an alternative to the nerve autograft avoiding the inevitable tissue damage caused at the graft donor site. Commercially available nerve repair conduits are currently only considered suitable for repairing small nerve lesions; the design and performance of engineered conduits requires significant improvements to enable their use for repairing larger nerve defects. Carbon nanotubes (CNTs) are an emerging novel material for biomedical applications currently being developed for a range of therapeutic technologies including scaffolds for engineering and interfacing with neurological tissues. CNTs possess a unique set of physicochemical properties that could be useful within nerve repair conduits. This progress report aims to evaluate and consolidate the current literature pertinent to CNTs as a biomaterial for supporting peripheral nerve regeneration. The report is presented in the context of the state‐of‐the‐art in nerve repair conduit design; outlining how CNTs may enhance the performance of next generation peripheral nerve repair conduits.

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The making of successful axonal regeneration: Genes, molecules and signal transduction pathways

Cited by 154 publications

References 289 publications

Enhanced Transmission at a Spinal Synapse TriggeredIn Vivoby an Injury Signal Independent of Altered Synaptic Activity

Enhanced Transmission at a Spinal Synapse TriggeredIn Vivoby an Injury Signal Independent of Altered Synaptic Activity

The Role of Timing in Nerve Reconstruction

Repairing Peripheral Nerves: Is there a Role for Carbon Nanotubes?

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