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Tessa Gordon - One of the best experts on this subject based on the ideXlab platform.
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the physiology of neural injury and regeneration the role of Neurotrophic Factors
Journal of Communication Disorders, 2010Co-Authors: Tessa GordonAbstract:Injured nerves regenerate slowly and often over long distances. Prolonged periods for regenerating nerves to make functional connections with denervated targets prolong the period of isolation of the neurons from the target (chronic axotomy) and of the denervation of Schwann cells in the distal nerve pathways (chronic denervation). In an animal model, we demonstrated that prolonged axotomy and chronic denervation severely reduce the regenerative capacity of neurons to less to 10%. Concurrent reduction in Neurotrophic Factors, including brain- and glial-derived Neurotrophic Factors (BDNF and GDNF) in axotomized neurons and denervated Schwann cells, suggest that these Factors are required to sustain nerve regeneration. Findings that exogenous BDNF and GDNF did not increase numbers of neurons that regenerate their axons in freshly cut and repaired rat nerves, but did increase the numbers significantly after chronic axotomy, are consistent with the view that there is sufficient endogenous Neurotrophic factor supply in axotomized motoneurons and denervated Schwann cells to support nerve regeneration but that the reduced supply must be supplemented when target reinnervation is delayed. In addition, findings that BDNF is essential for the effectiveness of brief low frequency electrical stimulation in promoting nerve growth, provides further support for a central role of BNDF in motor nerve regeneration. Learning outcomes: Readers of this article will gain an understanding of the basis for poor functional outcomes of peripheral nerve injuries, even when surgical repair is possible.
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the role of Neurotrophic Factors in nerve regeneration
Neurosurgical Focus, 2009Co-Authors: Tessa GordonAbstract:This review considers the 2 sources of Neurotrophic Factors in the peripheral nervous system (PNS), the neurons and the nonneuronal cells in the denervated distal nerve stumps, and their role in axon regeneration. Morphological assessment of regenerative success in response to administration of exogenous growth Factors after nerve injury and repair has indicated a role of the endogenous Neurotrophic Factors from Schwann cells in the distal nerve stump. However, the increased number of axons may reflect more neurons regenerating their axons and/or increased numbers of axon sprouts from the same number of neurons. Using fluorescent dyes to count neurons that regenerated their axons across a suture site and into distal nerve stumps, brain-derived Neurotrophic factor (BDNF) and glial cell–derived Neurotrophic factor (GDNF) were found not to increase the number of neurons that regenerated their axons after immediate nerve repair. Nevertheless, the Factors did reverse the deleterious effect of delayed nerve rep...
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Neurotrophic Factors and their receptors in axonal regeneration and functional recovery after peripheral nerve injury
Molecular Neurobiology, 2003Co-Authors: Gordon J Boyd, Tessa GordonAbstract:Over a half a century of research has confirmed that Neurotrophic Factors promote the survival and process outgrowth of isolated neurons in vitro. The mechanisms by which Neurotrophic Factors mediate these survival-promoting effects have also been well characterized. In vivo, peripheral neurons are critically dependent on limited amounts of Neurotrophic Factors during development. After peripheral nerve injury, the adult mammalian peripheral nervous system responds by making Neurotrophic Factors once again available, either by autocrine or paracrine sources. Three families of Neurotrophic Factors were compared, the neurotrophins, the GDNF family of Neurotrophic Factors, and the neuropoetic cytokines. Following a general overview of the mechanisms by which these Neurotrophic Factors mediate their effects, we reviewed the temporal pattern of expression of the Neurotrophic Factors and their receptors by axotomized motoneurons as well as in the distal nerve stump after peripheral nerve injury. We discussed recent experiments from our lab and others which have examined the role of Neurotrophic Factors in peripheral nerve injury. Although our understanding of the mechanisms by which Neurotrophic Factors mediate their effects in vivo are poorly understood, evidence is beginning to emerge that similar phenomena observed in vitro also apply to nerve regeneration in vivo.
Stephen B Mcmahon - One of the best experts on this subject based on the ideXlab platform.
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Therapeutic Potential of Neurotrophic Factors
From Neuroscience To Neurology, 2020Co-Authors: Stephen B Mcmahon, Beth B MurinsonAbstract:Publisher Summary The term “Neurotrophic factor” refers to the ability of a factor to nourish or support the growth of neurons and promote survival and growth of discrete subpopulations of neurons. Neurotrophic Factors may protect neurons against cytotoxic insults, and, moreover, Neurotrophic Factors may offer important therapeutic opportunities that go beyond promoting survival. This chapter also illustrates some of the neurobiological roles of Neurotrophic Factors in mature animals and discuss how, in some contexts a dysregulation of Neurotrophic factor expression may be an important contributor to the pathophysiological state. In these circumstances, a therapeutic potential exists for blocking particular Neurotrophic effects. There are a number of families of Neurotrophic Factors, but two in particular have been studied for their neuroprotective effects. These are neurotrophins and the glial cell line-derived Neurotrophic factor (GDNF) family. This chapter further reviews potential use of these Neurotrophic Factors in neurodegenerative disease.
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Neurotrophic Factors and their inhibitors in chronic pain treatment
Neurobiology of Disease, 2016Co-Authors: John D. Kelleher, Damini Tewari, Stephen B McmahonAbstract:Chronic pain affects more than 20% of the UK population. Neurotrophic Factors have been identified as therapeutic targets to improve current treatments of chronic pain. This review article focuses on nerve growth factor (NGF) and interleukin-6 (IL-6) as potential therapeutic targets. In this review we highlight the mechanisms of action and the current progress of targeted therapies in clinical trials.
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Neurotrophic Factors and neuropathic pain
Current Opinion in Pharmacology, 2001Co-Authors: Timothy J. Boucher, Stephen B McmahonAbstract:Abstract Neuropathic pain is a debilitating consequence of nerve damage. Existing treatment is largely ineffective. Current models of neuropathic pain recognise the importance of ectopic activity in primary sensory neurones impinging on a sensitised central nervous system. Neurotrophic Factors have been shown to be neuroprotective for damaged sensory neurones, providing a rationale for testing their effects in neuropathic pain states. Recent data have demonstrated potent analgesic effects of one factor (glial cell line-derived Neurotrophic factor) in animal models of neuropathy, and implicated changes in sodium channel α-subunits in the generation of afferent ectopic activity. The new findings provide a rational basis for the use of Neurotrophic Factors as a novel therapeutic treatment for neuropathic pain states.
Armin Blesch - One of the best experts on this subject based on the ideXlab platform.
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Neurotrophic Factors in combinatorial approaches for spinal cord regeneration
Cell and Tissue Research, 2012Co-Authors: Julianne Mccall, Norbert Weidner, Armin BleschAbstract:Axonal regeneration is inhibited by a plethora of different mechanisms in the adult central nervous system (CNS). While Neurotrophic Factors have been shown to stimulate axonal growth in numerous animal models of nervous system injury, a lack of suitable growth substrates, an insufficient activation of neuron-intrinsic regenerative programs, and extracellular inhibitors of regeneration limit the efficacy of Neurotrophic factor delivery for anatomical and functional recovery after spinal cord injury. Thus, growth-stimulating Factors will likely have to be combined with other treatment approaches to tap into the full potential of growth factor therapy for axonal regeneration. In addition, the temporal and spatial distribution of growth Factors have to be tightly controlled to achieve biologically active concentrations, to allow for the chemotropic guidance of axons, and to prevent adverse effects related to the widespread distribution of Neurotrophic Factors. Here, we will review the rationale for combinatorial treatments in axonal regeneration and summarize some recent progress in promoting axonal regeneration in the injured CNS using such approaches.
Frank Porreca - One of the best experts on this subject based on the ideXlab platform.
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Neurotrophic Factors as novel therapeutics for neuropathic pain
Nature Reviews Drug Discovery, 2003Co-Authors: Michael H Ossipo, Frank PorrecaAbstract:Neuropathic pain is a chronic condition that is caused by injury to the nervous system. Unlike acute pain, which is protective, neuropathic pain persists and serves no useful purpose, and severely affects quality of life. However, present therapies have modest efficacy in most patients, are palliative rather than curative, and their side effects represent significant limitations. Tremendous progress has been made over the past decade in our understanding of the biology of pain sensory neurons. The recent discovery that Neurotrophic Factors play an important role in neuropathic pain indicates that these pathways could serve as novel intervention points for therapy. Moreover, Neurotrophic Factors have the potential to address the underlying pathophysiology of neuropathic pain, thereby halting or reversing the disease process.
J. Thome - One of the best experts on this subject based on the ideXlab platform.
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Neurotrophic Factors and the pathophysiology of schizophrenic psychoses
European Psychiatry, 2004Co-Authors: Nuria Durany, J. ThomeAbstract:The aim of this review is to summarize the present state of findings on altered Neurotrophic factor levels in schizophrenic psychoses, on variations in genes coding for Neurotrophic Factors, and on the effect of antipsychotic drugs on the expression level of Neurotrophic Factors. This is a conceptual paper that aims to establish the link between the neuromaldevelopment theory of schizophrenia and Neurotrophic Factors. An extensive literature review has been done using the Pub Med database, a service of the National Library of Medicine, which includes over 14 million citations for biomedical articles back to the 1950s. The majority of studies discussed in this review support the notion of alterations of Neurotrophic Factors at the protein and gene level, respectively, and support the hypothesis that these alterations could, at least partially, explain some of the morphological, cytoarchitectural and neurobiochemical abnormalities found in the brain of schizophrenic patients. However, the results are not always conclusive and the clinical significance of these alterations is not fully understood. It is, thus, important to further Neurotrophic factor research in order to better understand the etiopathogenesis of schizophrenic psychoses and, thus, potentially develop new treatment strategies urgently needed for patients suffering from these devastating disorders.
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Neurotrophic Factors and the maldevelopmental hypothesis of schizophrenic psychoses
Journal of Neural Transmission, 1998Co-Authors: J. Thome, P. Foley, Peter RiedererAbstract:The maldevelopmental model of schizophrenia postulates pathological alterations in embryonal neurogenesis as the etiopathogenetic basis of schizophrenic psychosis; the Neurotrophic factor hypothesis explains these changes as the result of disturbances of processes involving the trophic Factors. Neurotransmitter deficits are thereby interpreted as epiphenomena of underlying Neurotrophic factor deficacy. The functional systems of the various Neurotrophic Factors are characterized by complex interaction mechanisms. Both primary genetic alterations, and secondary impairments, induced by exogene noxae, of the receptors and signal transducers associated with Neurotrophic Factors, as well as of the Neurotrophic Factors themselves are possible. Preliminary clinical studies indicate that schizophrenic psychoses may be associated with changes in the genetic code of certain Neurotrophic Factors. Various phenomena typical of the schizophrenic psychoses can be interpreted according to the Neurotrophic factor hypothesis.