Author
James W. Fawcett
Other affiliations: University of Sheffield, King's College London, National Institute for Medical Research ...read more
Bio: James W. Fawcett is an academic researcher from University of Cambridge. The author has contributed to research in topics: Axon & Perineuronal net. The author has an hindex of 100, co-authored 350 publications receiving 35525 citations. Previous affiliations of James W. Fawcett include University of Sheffield & King's College London.
Topics: Axon, Perineuronal net, Astrocyte, Regeneration (biology), Glial scar
Papers published on a yearly basis
Papers
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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
TL;DR: Deyelinated plaques in multiple sclerosis consists mostly of scar-type astrocytes and naked axons, but astroCytes inhibit the migration of both oligodendrocyte precursors and Schwann cells which must restrict their access to demyelinated axons.
1,833 citations
TL;DR: The mature ECM is thus inhibitory for experience-dependent plasticity, and degradation of CSPGs reactivates cortical plasticity.
Abstract: In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of the ECM is inhibitory for experience-dependent plasticity in the visual cortex. The organization of CSPGs into perineuronal nets coincided with the end of the critical period and was delayed by dark rearing. After CSPG degradation with chondroitinase-ABC in adult rats, monocular deprivation caused an ocular dominance shift toward the nondeprived eye. The mature ECM is thus inhibitory for experience-dependent plasticity, and degradation of CSPGs reactivates cortical plasticity.
1,518 citations
TL;DR: Far from being relatively minor aspects of neural development, regressive phenomena are now recognized as playing a major role in determining the form of the mature nervous system.
Abstract: The development of most regions of the vertebrate nervous system includes a distinct phase of neuronal degeneration during which a substantial proportion of the neurons initially generated die. This degeneration primarily adjusts the magnitude of each neuronal population to the size or functional needs of its projection field, but in the process it seems also to eliminate many neurons whose axons have grown to either the wrong target or an inappropriate region within the target area. In addition, many connections that are initially formed are later eliminated without the death of the parent cell. In most cases such process elimination results in the removal of terminal axonal branches and hence serves as a mechanism to "fine-tune" neuronal wiring. However, there are now also several examples of the large-scale elimination of early-formed pathways as a result of the selective degeneration of long axon collaterals. Thus, far from being relatively minor aspects of neural development, these regressive phenomena are now recognized as playing a major role in determining the form of the mature nervous system.
1,317 citations
TL;DR: Basal lamina grafts for reconnecting severed nerves are prepared from muscle by removing cellular material therefrom while preserving the tubular structure of the basal lamina, eventually reestablishing nerve function through the regenerated graft.
Abstract: Basal lamina grafts for reconnecting severed nerves are prepared from muscle by removing cellular material therefrom while preserving the tubular structure of the basal lamina. When connected to nerve stumps the basal lamina surfaces promote axon regeneration therethrough, eventually reestablishing nerve function through the regenerated graft.
965 citations
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or her own research.
Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or
7,563 citations
TL;DR: The effects of dominant-interfering or constitutively activated forms of various components of the JNK-p38 and ERK signaling pathways demonstrated that activation of JNK and p38 and concurrent inhibition of ERK are critical for induction of apoptosis in these cells.
Abstract: Apoptosis plays an important role during neuronal development, and defects in apoptosis may underlie various neurodegenerative disorders. To characterize molecular mechanisms that regulate neuronal apoptosis, the contributions to cell death of mitogen-activated protein (MAP) kinase family members, including ERK (extracellular signal-regulated kinase), JNK (c-JUN NH2-terminal protein kinase), and p38, were examined after withdrawal of nerve growth factor (NGF) from rat PC-12 pheochromocytoma cells. NGF withdrawal led to sustained activation of the JNK and p38 enzymes and inhibition of ERKs. The effects of dominant-interfering or constitutively activated forms of various components of the JNK-p38 and ERK signaling pathways demonstrated that activation of JNK and p38 and concurrent inhibition of ERK are critical for induction of apoptosis in these cells. Therefore, the dynamic balance between growth factor-activated ERK and stress-activated JNK-p38 pathways may be important in determining whether a cell survives or undergoes apoptosis.
5,398 citations
TL;DR: Data suggest that bcl-x plays an important role in both positive and negative regulation of programmed cell death, as well as in tissues containing long-lived postmitotic cells, such as adult brain.
3,172 citations
3,135 citations