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Lawrence D. F. Moon

Bio: Lawrence D. F. Moon is an academic researcher from Wolfson Centre for Age-Related Diseases. The author has contributed to research in topics: Spinal cord injury & Axon. The author has an hindex of 26, co-authored 63 publications receiving 6544 citations. Previous affiliations of Lawrence D. F. Moon include King's College London & Miami Project to Cure Paralysis.


Papers
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Journal ArticleDOI
11 Apr 2002-Nature
TL;DR: It is demonstrated that CSPGs are important inhibitory molecules in vivo and suggested that their manipulation will be useful for treatment of human spinal injuries.
Abstract: The inability of axons to regenerate after a spinal cord injury in the adult mammalian central nervous system (CNS) can lead to permanent paralysis. At sites of CNS injury, a glial scar develops, containing extracellular matrix molecules including chondroitin sulphate proteoglycans (CSPGs). CSPGs are inhibitory to axon growth in vitro, and regenerating axons stop at CSPG-rich regions in vivo. Removing CSPG glycosaminoglycan (GAG) chains attenuates CSPG inhibitory activity. To test the functional effects of degrading chondroitin sulphate (CS)-GAG after spinal cord injury, we delivered chondroitinase ABC (ChABC) to the lesioned dorsal columns of adult rats. We show that intrathecal treatment with ChABC degraded CS-GAG at the injury site, upregulated a regeneration-associated protein in injured neurons, and promoted regeneration of both ascending sensory projections and descending corticospinal tract axons. ChABC treatment also restored post-synaptic activity below the lesion after electrical stimulation of corticospinal neurons, and promoted functional recovery of locomotor and proprioceptive behaviours. Our results demonstrate that CSPGs are important inhibitory molecules in vivo and suggest that their manipulation will be useful for treatment of human spinal injuries.

2,150 citations

Journal ArticleDOI
TL;DR: It is predicted that combinations of strategies will lead to improvements in outcome after SCI, and that individual therapies are unlikely to provide a panacea.
Abstract: Spinal cord injury (SCI) can lead to paraplegia or quadriplegia. Although there are no fully restorative treatments for SCI, various rehabilitative, cellular and molecular therapies have been tested in animal models. Many of these have reached, or are approaching, clinical trials. Here, we review these potential therapies, with an emphasis on the need for reproducible evidence of safety and efficacy. Individual therapies are unlikely to provide a panacea. Rather, we predict that combinations of strategies will lead to improvements in outcome after SCI. Basic scientific research should provide a rational basis for tailoring specific combinations of clinical therapies to different types of SCI.

980 citations

Journal ArticleDOI
TL;DR: In this article, the authors present a series of linked editorials in the context of biomedical journal abstracts, including: http://onlinelibrary.wiley.com/doi/10.1111/bph.12954/abstract, http://Onlinelabel. wiley. com/doi /10.12956/ABstract, https://www.wired.org/content/index.cfm/
Abstract: Linked Editorials This Editorial is part of a series. To view the other Editorials in this series, visit: http://onlinelibrary.wiley.com/doi/10.1111/bph.12956/abstract; http://onlinelibrary.wiley.com/doi/10.1111/bph.12954/abstract; http://onlinelibrary.wiley.com/doi/10.1111/bph.12955/abstract and http://onlinelibrary.wiley.com/doi/10.1111/bph.13112/abstract

939 citations

Journal ArticleDOI
TL;DR: It is demonstrated that it is possible to enhance CNS axon regeneration in the adult rat nigrostriatal tract following chondroitinase ABC degradation of chondDetroitin sulfate.
Abstract: Following CNS injury in the adult mammal, axon regeneration fails in scar regions containing a number of different chondroitin sulfate-bearing proteoglycans (CSPGs)1. Degradation of chondroitin sulfate using chondroitinase ABC reduces growth inhibition associated with many CSPGs2,3,4,5,6,7,8,9,10,11,12,13. Here we demonstrate that it is possible to enhance CNS axon regeneration in the adult rat nigrostriatal tract following chondroitinase ABC degradation of chondroitin sulfate.

583 citations

Journal ArticleDOI
TL;DR: The chemokine CCL2, produced by both damaged and undamaged primary sensory neurons in neuropathic pain states in rats, is released in an activity dependent manner from the central terminals of these fibres and provides a mechanism for immune activation, which in turn regulates the sensitivity of pain signaling systems in neuropathy pain states.

296 citations


Cited by
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Journal ArticleDOI
19 Jun 2014-PeerJ
TL;DR: The advantages of open source to achieve the goals of the scikit-image library are highlighted, and several real-world image processing applications that use scik it-image are showcased.
Abstract: scikit-image is an image processing library that implements algorithms and utilities for use in research, education and industry applications. It is released under the liberal Modified BSD open source license, provides a well-documented API in the Python programming language, and is developed by an active, international team of collaborators. In this paper we highlight the advantages of open source to achieve the goals of the scikit-image library, and we showcase several real-world image processing applications that use scikit-image. More information can be found on the project homepage, http://scikit-image.org.

3,903 citations

PatentDOI
14 Nov 2002-Science
TL;DR: In this paper, pH-induced self-assembly of a peptide-amphiphile was used to make a nanostructured fibrous scaffold reminiscent of extracellular matrix.
Abstract: We have used the pH-induced self-assembly of a peptide-amphiphile to make a nanostructured fibrous scaffold reminiscent of extracellular matrix. The design of this peptide-amphiphile allows the nanofibers to be reversibly cross-linked to enhance or decrease their structural integrity. After cross-linking, the fibers are able to direct mineralization of hydroxyapatite to form a composite material in which the crystallographic c axes of hydroxyapatite are aligned with the long axes of the fibers. This alignment is the same as that observed between collagen fibrils and hydroxyapatite crystals in bone.

3,125 citations

Journal ArticleDOI
TL;DR: Chondroitin and keratan sulphate proteoglycans are among the main inhibitory extracellular matrix molecules that are produced by reactive astrocytes in the glial scar, and they are believed to play a crucial part in regeneration failure.
Abstract: After injury to the adult central nervous system (CNS), injured axons cannot regenerate past the lesion. In this review, we present evidence that this is due to the formation of a glial scar. Chondroitin and keratan sulphate proteoglycans are among the main inhibitory extracellular matrix molecules that are produced by reactive astrocytes in the glial scar, and they are believed to play a crucial part in regeneration failure. We will focus on this role, as well as considering the behaviour of regenerating neurons in the environment of CNS injury.

2,838 citations

01 Jan 2010
TL;DR: In this paper, the authors describe a scenario where a group of people are attempting to find a solution to the problem of "finding the needle in a haystack" in the environment.
Abstract: 中枢神経系疾患の治療は正常細胞(ニューロン)の機能維持を目的とするが,脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い.一方,脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める.いずれの場合にも,細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である.現在のところ最も研究の進んでいる細胞死の型はアポトーシスである.そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する.

2,716 citations

Journal ArticleDOI
11 Apr 2002-Nature
TL;DR: It is demonstrated that CSPGs are important inhibitory molecules in vivo and suggested that their manipulation will be useful for treatment of human spinal injuries.
Abstract: The inability of axons to regenerate after a spinal cord injury in the adult mammalian central nervous system (CNS) can lead to permanent paralysis. At sites of CNS injury, a glial scar develops, containing extracellular matrix molecules including chondroitin sulphate proteoglycans (CSPGs). CSPGs are inhibitory to axon growth in vitro, and regenerating axons stop at CSPG-rich regions in vivo. Removing CSPG glycosaminoglycan (GAG) chains attenuates CSPG inhibitory activity. To test the functional effects of degrading chondroitin sulphate (CS)-GAG after spinal cord injury, we delivered chondroitinase ABC (ChABC) to the lesioned dorsal columns of adult rats. We show that intrathecal treatment with ChABC degraded CS-GAG at the injury site, upregulated a regeneration-associated protein in injured neurons, and promoted regeneration of both ascending sensory projections and descending corticospinal tract axons. ChABC treatment also restored post-synaptic activity below the lesion after electrical stimulation of corticospinal neurons, and promoted functional recovery of locomotor and proprioceptive behaviours. Our results demonstrate that CSPGs are important inhibitory molecules in vivo and suggest that their manipulation will be useful for treatment of human spinal injuries.

2,150 citations