ResearchPad - spinal-cord https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Effect of experimental, morphological and mechanical factors on the murine spinal cord subjected to transverse contusion: A finite element study]]> https://www.researchpad.co/article/elastic_article_8463 Finite element models combined with animal experimental models of spinal cord injury provides the opportunity for investigating the effects of the injury mechanism on the neural tissue deformation and the resulting tissue damage. Thus, we developed a finite element model of the mouse cervical spinal cord in order to investigate the effect of morphological, experimental and mechanical factors on the spinal cord mechanical behavior subjected to transverse contusion. The overall mechanical behavior of the model was validated with experimental data of unilateral cervical contusion in mice. The effects of the spinal cord material properties, diameter and curvature, and of the impactor position and inclination on the strain distribution were investigated in 8 spinal cord anatomical regions of interest for 98 configurations of the model. Pareto analysis revealed that the material properties had a significant effect (p<0.01) for all regions of interest of the spinal cord and was the most influential factor for 7 out of 8 regions. This highlighted the need for comprehensive mechanical characterization of the gray and white matter in order to develop effective models capable of predicting tissue deformation during spinal cord injuries.

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<![CDATA[Microglia exit the CNS in spinal root avulsion]]> https://www.researchpad.co/article/5c79a3e5d5eed0c4841d1bf2

Microglia are central nervous system (CNS)-resident cells. Their ability to migrate outside of the CNS, however, is not understood. Using time-lapse imaging in an obstetrical brachial plexus injury (OBPI) model, we show that microglia squeeze through the spinal boundary and emigrate to peripheral spinal roots. Although both macrophages and microglia respond, microglia are the debris-clearing cell. Once outside the CNS, microglia re-enter the spinal cord in an altered state. These peripheral nervous system (PNS)-experienced microglia can travel to distal CNS areas from the injury site, including the brain, with debris. This emigration is balanced by two mechanisms—induced emigration via N-methyl-D-aspartate receptor (NMDA) dependence and restriction via contact-dependent cellular repulsion with macrophages. These discoveries open the possibility that microglia can migrate outside of their textbook-defined regions in disease states.

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<![CDATA[Localization of near-infrared labeled antibodies to the central nervous system in experimental autoimmune encephalomyelitis]]> https://www.researchpad.co/article/5c706776d5eed0c4847c7081

Antibodies, including antibodies to the RNA binding protein heterogeneous nuclear ribonucleoprotein A1, have been shown to contribute to the pathogenesis of multiple sclerosis, thus it is important to assess their biological activity using animal models of disease. Near-infrared optical imaging of fluorescently labeled antibodies and matrix metalloproteinase activity were measured and quantified in an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis. We successfully labeled, imaged and quantified the fluorescence signal of antibodies that localized to the central nervous system of mice with experimental autoimmune encephalomyelitis. Fluorescently labeled anti-heterogeneous nuclear ribonucleoprotein A1 antibodies persisted in the central nervous system of mice with experimental autoimmune encephalomyelitis, colocalized with matrix metalloproteinase activity, correlated with clinical disease and shifted rostrally within the spinal cord, consistent with experimental autoimmune encephalomyelitis being an ascending paralysis. The fluorescent antibody signal also colocalized with matrix metalloproteinase activity in brain. Previous imaging studies in experimental autoimmune encephalomyelitis analyzed inflammatory markers such as cellular immune responses, dendritic cell activity, blood brain barrier integrity and myelination, but none assessed fluorescently labeled antibodies within the central nervous system. This data suggests a strong association between autoantibody localization and disease. This system can be used to detect other antibodies that might contribute to the pathogenesis of autoimmune diseases of the central nervous system including multiple sclerosis.

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<![CDATA[Mental health in individuals with spinal cord injury: The role of socioeconomic conditions and social relationships]]> https://www.researchpad.co/article/5c76fe0dd5eed0c484e5b386

Objectives

To evaluate socioeconomic inequalities in social relationships, and to assess whether socioeconomic conditions and social relationships are independently related to mental health problems in individuals with a physical disability due to spinal cord injury (SCI).

Methods

We analyzed cross-sectional data from 511 individuals with SCI aged over 16 years who participated in the community survey of the Swiss SCI Cohort Study (SwiSCI). Indicators for socioeconomic conditions included years of formal education, household income, and financial strain. Social relationships were operationalized by three structural (partner status; social contact frequency; number of supportive relationships) and four functional aspects (satisfaction with: overall social support; family relationships; contacts to friends; partner relationship). General mental health was assessed by the Mental Health Inventory (MHI-5) of SF-36 and depressive symptoms were measured by the Hospital Anxiety and Depression Scale (depression subscale, HADS-D). Established cut-offs for general mental health problems (MHI-5 ≤56) and depressive symptomatology (HADS-D ≥8) were used to dichotomize outcomes. Associations were assessed using logistic regressions.

Results

Lower household income was predominantly associated with poor structural social relationships, whereas financial strain was robustly linked to poor functional social relationships. Financial strain was associated with general mental health problems and depressive symptomatology, even after controlling for social relationships. Education and household income were not linked to mental health. Poor structural and functional social relationships were related to general mental health problems and depressive symptomatology. Notably, trends remained stable after accounting for socioeconomic conditions.

Conclusion

This study provides evidence for socioeconomic inequalities in social relationships as well as for independent associations of financial strain and poor social relationships with mental health problems in individuals with SCI. Further research may develop strategies to improve mental health in SCI by strengthening social relationships. Such interventions may be especially beneficial for individuals with low income and financial strain.

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<![CDATA[Supported employment: Meta-analysis and review of randomized controlled trials of individual placement and support]]> https://www.researchpad.co/article/5c76fe41d5eed0c484e5b7ab

Supported employment is a treatment whereby those with severe mental illness (or other disabilities) receive aid searching for competitive employment and mental health (or other) treatments concurrently. The most popular implementation of supported employment is individual placement and support (IPS). We conducted meta-analytic analyses of the randomized controlled trials of IPS. We found that subjects in IPS, compared to usual treatment conditions, had better vocational outcomes (obtained any competitive employment: RR = 1.63, 95%CI = [1.46, 1.82]; job tenure: d = 0.55, 95%CI = [0.33, 0.79]; job length: d = 0.46, 95%CI = [0.35, 0.57]; income: d = 0.48, 95%CI = [0.36, 0.59]) Non-vocational outcomes estimates, while favoring IPS, included the null (quality of life: d = 0.30, 95%CI = [-0.07, 0.67]; global functioning: d = 0.09, 95%CI = [-0.09, 0.27]; mental health: d = 0.03, 95%CI = [-0.15, 0.21]). Analysis of the expected proportion of studies with a true effect on non-vocational outcomes with d>0.2 showed some reason to expect a possible improvement for quality of life for at least some settings (Prop = 0.57, 95%CI = [0.30, 0.84]).

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<![CDATA[Pressure redistributing in-seat movement activities by persons with spinal cord injury over multiple epochs]]> https://www.researchpad.co/article/5c6dc9fdd5eed0c48452a665

Pressure ulcers, by definition, are caused by external forces on the tissues, often in the regions of bony prominences. Wheelchair users are at risk to develop sitting-acquired pressure ulcers, which occur in the regions of the ischial tuberosities, sacrum/coccyx or greater trochanters. As a means to prevent pressure ulcers, instruction on performing pressure reliefs or weight shifts are a part of the rehabilitation process. The objective of this study was to monitor the weight shift activity of full-time wheelchair users with acute spinal cord injury over multiple epochs of time in order to determine consistency or routine within and across epochs. A second objective was to evaluate the accuracy of self-reported pressure relief frequency within each measurement epoch. A wheelchair in-seat activity monitor was used to measure weight shifts and other in-seat movement. The data was classified into multiple in-seat activity metrics using machine learning. Seventeen full-time wheelchair users with spinal cord injury were measured within multiple epochs, each lasting more than 1 week. Across all in-seat activity metrics, no consistent pattern of activity changes emerged. None of the in-seat activity metric changed in any one direction across a majority of subjects. Subjects tended to over-estimate their frequency of performing pressure reliefs. Self-reported pressure relief behaviors are not reliable, and therefore, cannot be used to evaluate preventative behaviors either clinically or within research. This study had the capability of fully investigating in-seat movements of wheelchair users. The results indicated that in-seat movement does not reflect a routine, either in pressure reliefs, weight shifts or other functional in-seat movements. This study has illustrated the complexity of assigning causation of pressure ulcer occurrence to seated behaviors of wheelchair users and identifies the need for improved clinical techniques designed to develop routine behaviors to prevent pressure ulcers.

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<![CDATA[The effect of endurance training and testosterone supplementation on the expression of blood spinal cord barrier proteins in rats]]> https://www.researchpad.co/article/5c6b2694d5eed0c484289cf8

The present study aimed to estimate the effect of endurance training, two doses of testosterone, and the combination of these stimuli on the level of the endothelial proteins claudin, occludin, JAM-1, VE-cadherin, ZO-1, ZO-2, and P-glycoprotein in rat spinal cords. Adult male Wistar rats were trained using a motor-driven treadmill for 6 weeks (40–60 min, 5 times per week) and/or were treated for 6 weeks with two doses of testosterone (i.m.; 8 mg/kg or 80 mg/kg body weight). Spinal cords were collected 48 hours after the last training cycle and stored at -80°C. The levels of selected proteins in whole tissue lysates of the spinal cord were measured by western blot. Testosterone-treated trained rats had significantly lower claudin levels than vehicle-treated trained rats. High doses of testosterone resulted in a significant decrease in claudin-5 in untrained rats compared to the control group. Both doses of testosterone significantly reduced occludin levels compared to those in vehicle-treated untrained rats. The JAM-1 level in the spinal cords of both trained and untrained animals receiving testosterone was decreased in a dose-dependent manner. The JAM-1 level in the trained group treated with high doses of testosterone was significantly higher than that in the untrained rats treated with 80 mg/kg of testosterone. VE-cadherin levels were decreased in all groups receiving testosterone regardless of endurance training and were also diminished in the vehicle-treated group compared to the control group. Testosterone treatment did not exert a significant effect on ZO-1 protein levels. Testosterone and/or training had no significant effects on ZO-2 protein levels in the rat spinal cords. Endurance training increased P-glycoprotein levels in the rat spinal cords. The results suggest that an excessive supply of testosterone may adversely impact the expression of endothelial proteins in the central nervous system, which, in turn, may affect the blood-brain barrier function.

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<![CDATA[Regenerative capacity in the lamprey spinal cord is not altered after a repeated transection]]> https://www.researchpad.co/article/5c5b52bbd5eed0c4842bcf38

The resilience of regeneration in vertebrates is not very well understood. Yet understanding if tissues can regenerate after repeated insults, and identifying limitations, is important for elucidating the underlying mechanisms of tissue plasticity. This is particularly challenging in tissues, such as the nervous system, which possess a large number of terminally differentiated cells and often exhibit limited regeneration in the first place. However, unlike mammals, which exhibit very limited regeneration of spinal cord tissues, many non-mammalian vertebrates, including lampreys, bony fishes, amphibians, and reptiles, regenerate their spinal cords and functionally recover even after a complete spinal cord transection. It is well established that lampreys undergo full functional recovery of swimming behaviors after a single spinal cord transection, which is accompanied by tissue repair at the lesion site, as well as axon and synapse regeneration. Here we begin to explore the resilience of spinal cord regeneration in lampreys after a second spinal transection (re-transection). We report that by all functional and anatomical measures tested, lampreys regenerate after spinal re-transection just as robustly as after single transections. Recovery of swimming, synapse and cytoskeletal distributions, axon regeneration, and neuronal survival were nearly identical after spinal transection or re-transection. Only minor differences in tissue repair at the lesion site were observed in re-transected spinal cords. Thus, regenerative potential in the lamprey spinal cord is largely unaffected by spinal re-transection, indicating a greater persistent regenerative potential than exists in some other highly regenerative models. These findings establish a new path for uncovering pro-regenerative targets that could be deployed in non-regenerative conditions.

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<![CDATA[Lactosylceramide synthases encoded by B4galt5 and 6 genes are pivotal for neuronal generation and myelin formation in mice]]> https://www.researchpad.co/article/5b8b29d640307c405292ca4e

It is uncertain which β4-galactosyltransferase (β4GalT; gene name, B4galt), β4GalT-5 and/or β4GalT-6, is responsible for the production of lactosylceramide (LacCer) synthase, which functions in the initial step of ganglioside biosynthesis. Here, we generated conditional B4galt5 knockout (B4galt5 cKO) mice, using Nestin-Cre mice, and crossed these with B4galt6 KO mice to generate B4galt5 and 6 double KO (DKO) mice in the central nervous system (CNS). LacCer synthase activity and major brain gangliosides were completely absent in brain homogenates from the DKO mice, although LacCer synthase activity was about half its normal level in B4galt5 cKO mice and B4galt6 KO mice. The DKO mice were born normally but they showed growth retardation and motor deficits at 2 weeks and died by 4 weeks of age. Histological analyses showed that myelin-associated proteins were rarely found localized in axons in the cerebral cortex, and axonal and myelin formation were remarkably impaired in the spinal cords of the DKO mice. Neuronal cells, differentiated from neurospheres that were prepared from the DKO mice, showed impairments in neurite outgrowth and branch formation, which can be explained by the fact that neurospheres from DKO mice could weakly interact with laminin due to lack of gangliosides, such as GM1a. Furthermore, the neurons were immature and perineuronal nets (PNNs) were poorly formed in DKO cerebral cortices. Our results indicate that LacCer synthase is encoded by B4galt5 and 6 genes in the CNS, and that gangliosides are indispensable for neuronal maturation, PNN formation, and axonal and myelin formation.

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<![CDATA[A scoping review of biopsychosocial risk factors and co-morbidities for common spinal disorders]]> https://www.researchpad.co/article/5b28b3fe463d7e129299938d

Objective

The purpose of this review was to identify risk factors, prognostic factors, and comorbidities associated with common spinal disorders.

Methods

A scoping review of the literature of common spinal disorders was performed through September 2016. To identify search terms, we developed 3 terminology groups for case definitions: 1) spinal pain of unknown origin, 2) spinal syndromes, and 3) spinal pathology. We used a comprehensive strategy to search PubMed for meta-analyses and systematic reviews of case-control studies, cohort studies, and randomized controlled trials for risk and prognostic factors and cross-sectional studies describing associations and comorbidities.

Results

Of 3,453 candidate papers, 145 met study criteria and were included in this review. Risk factors were reported for group 1: non-specific low back pain (smoking, overweight/obesity, negative recovery expectations), non-specific neck pain (high job demands, monotonous work); group 2: degenerative spinal disease (workers’ compensation claim, degenerative scoliosis), and group 3: spinal tuberculosis (age, imprisonment, previous history of tuberculosis), spinal cord injury (age, accidental injury), vertebral fracture from osteoporosis (type 1 diabetes, certain medications, smoking), and neural tube defects (folic acid deficit, anti-convulsant medications, chlorine, influenza, maternal obesity). A range of comorbidities was identified for spinal disorders.

Conclusion

Many associated factors for common spinal disorders identified in this study are modifiable. The most common spinal disorders are co-morbid with general health conditions, but there is a lack of clarity in the literature differentiating which conditions are merely comorbid versus ones that are risk factors. Modifiable risk factors present opportunities for policy, research, and public health prevention efforts on both the individual patient and community levels. Further research into prevention interventions for spinal disorders is needed to address this gap in the literature.

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<![CDATA[From Spontaneous Motor Activity to Coordinated Behaviour: A Developmental Model]]> https://www.researchpad.co/article/5989dabeab0ee8fa60bafde8

In mammals, the developmental path that links the primary behaviours observed during foetal stages to the full fledged behaviours observed in adults is still beyond our understanding. Often theories of motor control try to deal with the process of incremental learning in an abstract and modular way without establishing any correspondence with the mammalian developmental stages. In this paper, we propose a computational model that links three distinct behaviours which appear at three different stages of development. In order of appearance, these behaviours are: spontaneous motor activity (SMA), reflexes, and coordinated behaviours, such as locomotion. The goal of our model is to address in silico four hypotheses that are currently hard to verify in vivo: First, the hypothesis that spinal reflex circuits can be self-organized from the sensor and motor activity induced by SMA. Second, the hypothesis that supraspinal systems can modulate reflex circuits to achieve coordinated behaviour. Third, the hypothesis that, since SMA is observed in an organism throughout its entire lifetime, it provides a mechanism suitable to maintain the reflex circuits aligned with the musculoskeletal system, and thus adapt to changes in body morphology. And fourth, the hypothesis that by changing the modulation of the reflex circuits over time, one can switch between different coordinated behaviours. Our model is tested in a simulated musculoskeletal leg actuated by six muscles arranged in a number of different ways. Hopping is used as a case study of coordinated behaviour. Our results show that reflex circuits can be self-organized from SMA, and that, once these circuits are in place, they can be modulated to achieve coordinated behaviour. In addition, our results show that our model can naturally adapt to different morphological changes and perform behavioural transitions.

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<![CDATA[Glial Tumor Necrosis Factor Alpha (TNFα) Generates Metaplastic Inhibition of Spinal Learning]]> https://www.researchpad.co/article/5989db12ab0ee8fa60bcc71d

Injury-induced overexpression of tumor necrosis factor alpha (TNFα) in the spinal cord can induce chronic neuroinflammation and excitotoxicity that ultimately undermines functional recovery. Here we investigate how TNFα might also act to upset spinal function by modulating spinal plasticity. Using a model of instrumental learning in the injured spinal cord, we have previously shown that peripheral intermittent stimulation can produce a plastic change in spinal plasticity (metaplasticity), resulting in the prolonged inhibition of spinal learning. We hypothesized that spinal metaplasticity may be mediated by TNFα. We found that intermittent stimulation increased protein levels in the spinal cord. Using intrathecal pharmacological manipulations, we showed TNFα to be both necessary and sufficient for the long-term inhibition of a spinal instrumental learning task. These effects were found to be dependent on glial production of TNFα and involved downstream alterations in calcium-permeable AMPA receptors. These findings suggest a crucial role for glial TNFα in undermining spinal learning, and demonstrate the therapeutic potential of inhibiting TNFα activity to rescue and restore adaptive spinal plasticity to the injured spinal cord. TNFα modulation represents a novel therapeutic target for improving rehabilitation after spinal cord injury.

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<![CDATA[The Glial Scar-Monocyte Interplay: A Pivotal Resolution Phase in Spinal Cord Repair]]> https://www.researchpad.co/article/5989da12ab0ee8fa60b79e4d

The inflammatory response in the injured spinal cord, an immune privileged site, has been mainly associated with the poor prognosis. However, recent data demonstrated that, in fact, some leukocytes, namely monocytes, are pivotal for repair due to their alternative anti-inflammatory phenotype. Given the pro-inflammatory milieu within the traumatized spinal cord, known to skew monocytes towards a classical phenotype, a pertinent question is how parenchymal-invading monocytes acquire resolving properties essential for healing, under such unfavorable conditions. In light of the spatial association between resolving (interleukin (IL)-10 producing) monocytes and the glial scar matrix chondroitin sulfate proteoglycan (CSPG), in this study we examined the mutual relationship between these two components. By inhibiting the de novo production of CSPG following spinal cord injury, we demonstrated that this extracellular matrix, mainly known for its ability to inhibit axonal growth, serves as a critical template skewing the entering monocytes towards the resolving phenotype. In vitro cell culture studies demonstrated that this matrix alone is sufficient to induce such monocyte polarization. Reciprocal conditional ablation of the monocyte-derived macrophages concentrated at the lesion margins, using diphtheria toxin, revealed that these cells have scar matrix-resolving properties. Replenishment of monocytic cell populations to the ablated mice demonstrated that this extracellular remodeling ability of the infiltrating monocytes requires their expression of the matrix-degrading enzyme, matrix metalloproteinase 13 (MMP-13), a property that was found here to be crucial for functional recovery. Altogether, this study demonstrates that the glial scar-matrix, a known obstacle to regeneration, is a critical component skewing the encountering monocytes towards a resolving phenotype. In an apparent feedback loop, monocytes were found to regulate scar resolution. This cross-regulation between the glial scar and monocytes primes the resolution of this interim phase of spinal cord repair, thereby providing a fundamental platform for the dynamic healing response.

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<![CDATA[Effects of Constant and Doublet Frequency Electrical Stimulation Patterns on Force Production of Knee Extensor Muscles]]> https://www.researchpad.co/article/5989da09ab0ee8fa60b7708d

This study compared knee extensors’ neuromuscular fatigue in response to two 30-minute stimulation patterns: constant frequency train (CFT) and doublet frequency train (DFT). Fifteen men underwent two separate sessions corresponding to each pattern. Measurements included torque evoked by each contraction and maximal voluntary contractions (MVC) measured before and immediately after the stimulation sessions. In addition, activation level and torque evoked during doublets (Pd) and tetanic contractions at 80-Hz (P80) and 20-Hz (P20) were determined in six subjects. Results indicated greater mean torque during the DFT stimulation session as compared with CFT. But, no difference was obtained between the two stimulation patterns for MVC and evoked torque decreases. Measurements conducted in the subgroup depicted a significant reduction of Pd, P20 and P80. Statistical analyses also revealed bigger P20 immediate reductions after CFT than after DFT. We concluded that DFT could be a useful stimulation pattern to produce and maintain greater force with quite similar fatigue than CFT.

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<![CDATA[The C-Terminal Domains of NF-H and NF-M Subunits Maintain Axonal Neurofilament Content by Blocking Turnover of the Stationary Neurofilament Network]]> https://www.researchpad.co/article/5989da30ab0ee8fa60b842aa

Newly synthesized neurofilaments or protofilaments are incorporated into a highly stable stationary cytoskeleton network as they are transported along axons. Although the heavily phosphorylated carboxyl-terminal tail domains of the heavy and medium neurofilament (NF) subunits have been proposed to contribute to this process and particularly to stability of this structure, their function is still obscure. Here we show in NF-H/M tail deletion [NF-(H/M)tailΔ] mice that the deletion of both of these domains selectively lowers NF levels 3–6 fold along optic axons without altering either rates of subunit synthesis or the rate of slow axonal transport of NF. Pulse labeling studies carried out over 90 days revealed a significantly faster rate of disappearance of NF from the stationary NF network of optic axons in NF-(H/M)tailΔ mice. Faster NF disappearance was accompanied by elevated levels of NF-L proteolytic fragments in NF-(H/M)tailΔ axons. We conclude that NF-H and NF-M C-terminal domains do not normally regulate NF transport rates as previously proposed, but instead increase the proteolytic resistance of NF, thereby stabilizing the stationary neurofilament cytoskeleton along axons.

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<![CDATA[The Multifaceted Effects of Agmatine on Functional Recovery after Spinal Cord Injury through Modulations of BMP-2/4/7 Expressions in Neurons and Glial Cells]]> https://www.researchpad.co/article/5989da9eab0ee8fa60ba4b55

Presently, few treatments for spinal cord injury (SCI) are available and none have facilitated neural regeneration and/or significant functional improvement. Agmatine (Agm), a guanidinium compound formed from decarboxylation of L-arginine by arginine decarboxylase, is a neurotransmitter/neuromodulator and been reported to exert neuroprotective effects in central nervous system injury models including SCI. The purpose of this study was to demonstrate the multifaceted effects of Agm on functional recovery and remyelinating events following SCI. Compression SCI in mice was produced by placing a 15 g/mm2 weight for 1 min at thoracic vertebra (Th) 9 segment. Mice that received an intraperitoneal (i.p.) injection of Agm (100 mg/kg/day) within 1 hour after SCI until 35 days showed improvement in locomotor recovery and bladder function. Emphasis was made on the analysis of remyelination events, neuronal cell preservation and ablation of glial scar area following SCI. Agm treatment significantly inhibited the demyelination events, neuronal loss and glial scar around the lesion site. In light of recent findings that expressions of bone morphogenetic proteins (BMPs) are modulated in the neuronal and glial cell population after SCI, we hypothesized whether Agm could modulate BMP- 2/4/7 expressions in neurons, astrocytes, oligodendrocytes and play key role in promoting the neuronal and glial cell survival in the injured spinal cord. The results from computer assisted stereological toolbox analysis (CAST) demonstrate that Agm treatment dramatically increased BMP- 2/7 expressions in neurons and oligodendrocytes. On the other hand, BMP- 4 expressions were significantly decreased in astrocytes and oligodendrocytes around the lesion site. Together, our results reveal that Agm treatment improved neurological and histological outcomes, induced oligodendrogenesis, protected neurons, and decreased glial scar formation through modulating the BMP- 2/4/7 expressions following SCI.

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<![CDATA[Magnetic Resonance Imaging in Multiple Sclerosis – Patients' Experiences, Information Interests and Responses to an Education Programme]]> https://www.researchpad.co/article/5989da87ab0ee8fa60b9c900

Background

Magnetic resonance imaging (MRI) is a key diagnostic and monitoring tool in multiple sclerosis (MS) management. However, many scientific uncertainties, especially concerning correlates to impairment and prognosis remain. Little is known about MS patients' experiences, knowledge, attitudes, and unmet information needs concerning MRI.

Methods

We performed qualitative interviews (n = 5) and a survey (n = 104) with MS patients regarding MRI patient information, and basic MRI knowledge. Based on these findings an interactive training program of 2 hours was developed and piloted in n = 26 patients.

Results

Interview analyses showed that patients often feel lost in the MRI scanner and left alone with MRI results and images while 90% of patients in the survey expressed a high interest in MRI education. Knowledge on MRI issues was fair with some important knowledge gaps. Major information interests were relevance of lesions as well as the prognostic and diagnostic value of MRI results. The education program was highly appreciated and resulted in a substantial knowledge increase. Patients reported that, based on the program, they felt more competent to engage in encounters with their physicians.

Conclusion

This work strongly supports the further development of an evidence-based MRI education program for MS patients to enhance participation in health-care.

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<![CDATA[VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies]]> https://www.researchpad.co/article/5989da89ab0ee8fa60b9d296

VGF mRNA is widely expressed in areas of the nervous system known to degenerate in Amyotrophic Lateral Sclerosis (ALS), including cerebral cortex, brainstem and spinal cord. Despite certain VGF alterations are reported in animal models, little information is available with respect to the ALS patients. We addressed VGF peptide changes in fibroblast cell cultures and in plasma obtained from ALS patients, in parallel with spinal cord and plasma samples from the G93A-SOD1 mouse model. Antisera specific for the C-terminal end of the human and mouse VGF proteins, respectively, were used in immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), while gel chromatography and HPLC/ESI-MS/MS were used to identify the VGF peptides present. Immunoreactive VGF C-terminus peptides were reduced in both fibroblast and plasma samples from ALS patients in an advanced stage of the disease. In the G93A-SOD1 mice, the same VGF peptides were also decreased in plasma in the late-symptomatic stage, while showing an earlier down-regulation in the spinal cord. In immunohistochemistry, a large number of gray matter structures were VGF C-terminus immunoreactive in control mice (including nerve terminals, axons and a few perikarya identified as motoneurons), with a striking reduction already in the pre-symptomatic stage. Through gel chromatography and spectrometry analysis, we identified one form likely to be the VGF precursor as well as peptides containing the NAPP- sequence in all tissues studied, while in the mice and fibroblasts, we revealed also AQEE- and TLQP- peptides. Taken together, selective VGF fragment depletion may participate in disease onset and/or progression of ALS.

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<![CDATA[A Role for Neuropilins in the Interaction between Schwann Cells and Meningeal Cells]]> https://www.researchpad.co/article/5989d9e9ab0ee8fa60b6c37f

In their natural habitat, the peripheral nerve, Schwann cells (SCs) form nicely aligned pathways (also known as the bands of Büngner) that guide regenerating axons to their targets. Schwann cells that are implanted in the lesioned spinal cord fail to align in pathways that could support axon growth but form cellular clusters that exhibit only limited intermingling with the astrocytes and meningeal cells (MCs) that are present in the neural scar. The formation of cell clusters can be studied in co-cultures of SCs and MCs. In these co-cultures SCs form cluster-like non-overlapping cell aggregates with well-defined boundaries. There are several indications that neuropilins (NRPs) play an important role in MC-induced SC aggregation. Both SCs and MCs express NRP1 and NRP2 and SCs express the NRP ligands Sema3B, C and E while MCs express Sema3A, C, E and F. We now demonstrate that in SC-MC co-cultures, siRNA mediated knockdown of NRP2 in SCs decreased the formation of SC clusters while these SCs maintained their capacity to align in bands of Büngner-like columnar arrays. Unexpectedly, knockdown of NRP1 expression resulted in a significant increase in SC aggregation. These results suggest that a reduction in NRP2 expression may enhance the capacity of implanted SCs to interact with MCs that invade a neural scar formed after a lesion of the spinal cord.

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<![CDATA[Novel insights into SLC25A46-related pathologies in a genetic mouse model]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf253

The mitochondrial protein SLC25A46 has been recently identified as a novel pathogenic cause in a wide spectrum of neurological diseases, including inherited optic atrophy, Charcot-Marie-Tooth type 2, Leigh syndrome, progressive myoclonic ataxia and lethal congenital pontocerebellar hypoplasia. SLC25A46 is an outer membrane protein, member of the Solute Carrier 25 (SLC25) family of nuclear genes encoding mitochondrial carriers, with a role in mitochondrial dynamics and cristae maintenance. Here we identified a loss-of-function mutation in the Slc25a46 gene that causes lethal neuropathology in mice. Mutant mice manifest the main clinical features identified in patients, including ataxia, optic atrophy and cerebellar hypoplasia, which were completely rescued by expression of the human ortholog. Histopathological analysis revealed previously unseen lesions, most notably disrupted cytoarchitecture in the cerebellum and retina and prominent abnormalities in the neuromuscular junction. A distinct lymphoid phenotype was also evident. Our mutant mice provide a valid model for understanding the mechanistic basis of the complex SLC25A46-mediated pathologies, as well as for screening potential therapeutic interventions.

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