Journal of neurotrauma
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Progress in promoting axonal plasticity and regeneration in animal models of spinal cord injury (SCI) has led to novel prospects for the initiation of human clinical trials in the near future. This review discusses a number of considerations in the path to translating a preclinical candidate from the laboratory to clinical testing. We will also briefly discuss issues associated with the design, performance, analysis, and reporting of human clinical trials in SCI. It is important, for both the medical community and the spinal cord injured community, that objective scientific and medical standards are adopted in the clinical translation of potentially promising, but as yet unproven, therapies for SCI.
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Journal of neurotrauma · Mar 2006
Decorin promotes plasminogen/plasmin expression within acute spinal cord injuries and by adult microglia in vitro.
Spinal cord scar tissue presents a combined physical and molecular barrier to axon regeneration. Theoretically, spinal cord injuries (SCIs) can be rendered more permissive to axon growth by either suppressing synthesis of misaligned, fibrotic scar tissue and associated axon growth inhibitors, or enzymatically degrading them. We have previously shown that acute infusion of human recombinant decorin core protein into discreet stab injuries of the rat dorsal column pathways effected a major suppression of inflammation, astrogliosis, and multiple axon growth inhibitory chondroitin sulfate proteoglycans, which combined to promote rapid axon growth across the injury site. ⋯ Infusion of hr-decorin over the first 8 days post-SCI induced 10- and 17-fold increases in plasminogen and plasmin protein levels, respectively, within sites of injury and a threefold increase in microglial plasminogen mRNA in vitro. In addition to potentially degrading multiple axon growth inhibitory components of the glial scar, plasmin is known to play major roles in activating neurotrophins and promoting central nervous system (CNS) plasticity. The wider implications of decorin induction of plasmin in the injured spinal cord for axon regeneration, and recovery of function at acute and chronic time points post-SCI are reviewed.
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Myelin of the adult mammalian central nervous system (CNS) has been attributed to suppress structural plasticity and to impede regenerating nerve fibers. Nogo-A is possibly the best characterized of a variety of neurite growth inhibitors present in CNS myelin. Neutralizing its activity results in improved axon regrowth and functional recovery in experimental CNS lesion models of adult rodents and primates. While Nogo-A has become a major target for therapeutic intervention to promote axon regeneration in the CNS, it is realized that such an approach will likely have to be combined with other therapeutic strategies to maximize functional recovery after spinal cord injury (SCI).
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Journal of neurotrauma · Feb 2006
ReviewA Web-based systematic review on traumatic spinal cord injury comparing the "citation classics" with the consumers' perspectives.
Although the citation index of an article is not a direct measure of its quality or importance, it is a measure of recognition that may suggest its impact on the scientific community. This study was undertaken to examine the characteristics of the top 100 most frequently cited articles (so-called "citation classics") on traumatic spinal cord injury (SCI) that were published between 1986 and 2003, and to compare this selected professional literature with the consumers' perspective on the key issues in SCI research. The 100 top-cited articles on traumatic SCI were identified using the Internet database of the Science Citation Index Expanded and the Web of Science with the terms "spinal cord injury" and "spinal cord injuries." Meeting abstracts, letters, and editorials were excluded. ⋯ This bibliometric analysis, for the first time, identifies the key features of the citation classics on traumatic SCI between 1986 and 2003, a period that represents one of an unprecedented increase in knowledge in this field. The 100 top-cited peer-reviewed articles have been predominantly focused on basic science SCI research indicating a need for greater bench-to-bedside translational studies in SCI research. Although the body of this top-cited professional literature mostly matches with the consumers' perspective, most of this research has been focused on motor function assessment and recovery following SCI.
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Epilepsy is a major unfavorable long-term consequence of traumatic brain injury (TBI). Moreover, TBI is one of the most important predisposing factors for the development of epilepsy, particularly in young adults. ⋯ The goal of this review is to (1) provide a description of PTE in humans, which is critical for the development of clinically relevant models of PTE, (2) review the characteristics of currently available PTE models, and (3) provide suggestions for the development of future models of PTE based on our current understanding of the mechanisms of TBI and epilepsy. The development of clinically relevant models of PTE is critical to advance our understanding of the mechanisms of post-traumatic epileptogenesis and epilepsy, as well as for producing breakthroughs in the development and testing of novel antiepileptogenic treatments.