Experimental neurology
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Experimental neurology · Oct 2013
Complementary roles of different oscillatory activities in the subthalamic nucleus in coding motor effort in Parkinsonism.
The basal ganglia may play an important role in the control of motor scaling or effort. Recently local field potential (LFP) recordings from patients with deep brain stimulation electrodes in the basal ganglia have suggested that local increases in the synchronisation of neurons in the gamma frequency band may correlate with force or effort. Whether this feature uniquely codes for effort and whether such a coding mechanism holds true over a range of efforts is unclear. ⋯ Accordingly, the difference between power changes in the gamma and beta bands correlated with effort across all effort levels. These findings suggest complementary roles for changes in beta and gamma band activities in the STN in motor effort coding. The latter function is thought to be impaired in untreated PD where task-related reactivity in these two bands is deficient.
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Experimental neurology · Oct 2013
A re-assessment of the effects of treatment with a non-steroidal anti-inflammatory (ibuprofen) on promoting axon regeneration via RhoA inhibition after spinal cord injury.
This study was undertaken as part of the NIH "Facilities of Research Excellence-Spinal Cord Injury" project to support independent replication of published studies. Here, we repeat key parts of a study reporting that rats treated with ibuprofen via subcutaneous minipump exhibited greater recovery of motor function and enhanced axonal growth after spinal cord injury. We carried out 3 separate experiments in which young adult female Sprague-Dawley rats received dorsal over-hemisections at T6-T7, and then were implanted with osmotic minipumps for subcutaneous delivery of ibuprofen or saline. ⋯ Rats that received Ibuprofen did not demonstrate statistically significant improvements in bladder function. Quantitative analyses of CST and 5HT axon distribution also did not reveal differences between ibuprofen-treated and control rats. Taken together, our results only partially replicate the findings that treatment with ibuprofen improves motor function after SCI but fail to replicate findings regarding enhanced axon growth.
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Experimental neurology · Oct 2013
Modeling clinically relevant blast parameters based on scaling principles produces functional & histological deficits in rats.
Blast-induced traumatic brain injury represents a leading cause of injury in modern warfare with injury pathogenesis poorly understood. Preclinical models of blast injury remain poorly standardized across laboratories and the clinical relevance unclear based upon pulmonary injury scaling laws. Models capable of high peak overpressures and of short duration may better replicate clinical exposure when scaling principles are considered. ⋯ Furthermore, hematoxylin and eosin staining showed the presence of red blood cells within the parenchyma and red, swollen neurons following blast injury. Exposure to blast with 90.10 PSI peak reflected overpressure resulted in immediate mortality associated with extensive intracranial bleeding. This work demonstrates one of the first examples of blast-induced brain injury in the rodent when exposed to a blast wave scaled from human exposure based on scaling principles derived from pulmonary injury lethality curves.
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Experimental neurology · Oct 2013
Comparative StudyA comparison of the behavioral and anatomical outcomes in sub-acute and chronic spinal cord injury models following treatment with human mesenchymal precursor cell transplantation and recombinant decorin.
This study assessed the potential of highly purified (Stro-1(+)) human mesenchymal precursor cells (hMPCs) in combination with the anti-scarring protein decorin to repair the injured spinal cord (SC). Donor hMPCs isolated from spinal cord injury (SCI) patients were transplanted into athymic rats as a suspension graft, alone or after previous treatment with, core (decorin(core)) and proteoglycan (decorin(pro)) isoforms of purified human recombinant decorin. Decorin was delivered via mini-osmotic pumps for 14 days following sub-acute (7 day) or chronic (1 month) SCI. hMPCs were delivered to the spinal cord at 3 weeks or 6 weeks after the initial injury at T9 level. ⋯ Decorin did not increase axonal outgrowth from that achieved by hMPCs. We provide evidence for the first time that (Stro-1(+)) hMPCs provide: i) an advantageous source of allografts for stem cell transplantation for sub-acute and chronic spinal cord therapy, and (ii) a positive host microenvironment that promotes tissue sparing/repair that subsequently improves behavioral outcomes after SCI. This was not measurably improved by recombinant decorin treatment, but does provide important information for the future development and potential use of decorin in contusive SCI therapy.
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Experimental neurology · Oct 2013
Canine degenerative myelopathy: biochemical characterization of superoxide dismutase 1 in the first naturally occurring non-human amyotrophic lateral sclerosis model.
Mutations in canine superoxide dismutase 1 (SOD1) have recently been shown to cause canine degenerative myelopathy, a disabling neurodegenerative disorder affecting specific breeds of dogs characterized by progressive motor neuron loss and paralysis until death, or more common, euthanasia. This discovery makes canine degenerative myelopathy the first and only naturally occurring non-human model of amyotrophic lateral sclerosis (ALS), closely paralleling the clinical, pathological, and genetic presentation of its human counterpart, SOD1-mediated familial ALS. To further understand the biochemical role that canine SOD1 plays in this disease and how it may be similar to human SOD1, we characterized the only two SOD1 mutations described in affected dogs to date, E40K and T18S. ⋯ Further studies show that these mutants, like most human SOD1 mutants, have an increased propensity to form aggregates in cell culture, with 10-20% of cells possessing visible aggregates. Creation of the E40K mutation in human SOD1 recapitulates the normal enzymatic activity but not the aggregation propensity seen with the canine mutant. Our findings lend strong biochemical support to the toxic role of SOD1 in canine degenerative myelopathy and establish close parallels for the role mutant SOD1 plays in both canine and human disorders.