Journal of neurotrauma
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Journal of neurotrauma · May 2006
Comparative StudyBasso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains.
Genetically engineered mice are used extensively to examine molecular responses to spinal cord injury (SCI). Inherent strain differences may confound behavioral outcomes; therefore, behavioral characterization of several strains after SCI is warranted. The Basso, Beattie, Bresnahan Locomotor Rating Scale (BBB) for rats has been widely used for SCI mice, but may not accurately reflect their unique recovery pattern. ⋯ BMS revealed significantly higher recovery in C57BL/10, B10. PL and F1 than the C57BL/6 and BALB/c strains after moderate SCI (p < 0.05). The differing behavioral response to SCI suggests inherent genetic factors significantly impact locomotor recovery and must be considered in studies with inbred or genetically engineered mouse strains.
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Journal of neurotrauma · May 2006
Postinjury administration of pituitary adenylate cyclase activating polypeptide (PACAP) attenuates traumatically induced axonal injury in rats.
Pituitary adenylate cyclase activating polypeptide (PACAP) has several different actions in the nervous system. Numerous studies have shown its neuroprotective effects both in vitro and in vivo. Previously, it has been demonstrated that PACAP reduces brain damage in rat models of global and focal cerebral ischemia. ⋯ There was no significant difference between the density of beta-APP-immunopositive axons in the medial longitudinal fascicle (MLF). PACAP treatment did not result in significantly different number of RMO-14-immunopositive axonal profiles in either brain areas 2 hours post-injury compared to normal animals. While the results of this study highlighted the complexity of the pathogenesis and manifestation of diffuse axonal injury, they also indicate that PACAP should be considered a potential therapeutic agent in TBI.
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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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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 · 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.