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Brain Sci., Volume 7, Issue 2 (February 2017)

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Research

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Open AccessArticle NLRP12 Inflammasome Expression in the Rat Brain in Response to LPS during Morphine Tolerance
Brain Sci. 2017, 7(2), 14; doi:10.3390/brainsci7020014
Received: 22 June 2016 / Revised: 11 January 2017 / Accepted: 16 January 2017 / Published: 6 February 2017
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Abstract
Morphine, an effective but addictive analgesic, can profoundly affect the inflammatory response to pathogens, and long-term use can result in morphine tolerance. Inflammasomes are protein complexes involved in the inflammatory response. The nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing (NLRP) 12
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Morphine, an effective but addictive analgesic, can profoundly affect the inflammatory response to pathogens, and long-term use can result in morphine tolerance. Inflammasomes are protein complexes involved in the inflammatory response. The nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing (NLRP) 12 (NLRP12) inflammasome has been reported to have anti-inflammatory activity. In this study, we examined the expression of NLRP12 inflammasome related genes in the adult F344 rat brain in response to the bacterial endotoxin lipopolysaccharide (LPS) in the presence and absence of morphine tolerance. Morphine tolerance was elicited using the 2 + 4 morphine-pelleting protocol. On Day 1, the rats were pelleted subcutaneously with 2 pellets of morphine (75 mg/pellet) or a placebo; on Days 2 and 4 pellets were given. On Day 5, the animals were randomly assigned to receive either 250 µg/kg LPS or saline (i.p.). The expression of 84 inflammasome related genes in the rat brain was examined using a Ploymerase Chain Reaction (PCR) array. In response to LPS, there was a significant increase in the expression of the pro-inflammatory cytokine/chemokine genes interleukin-1 beta (Il-1β), interleukin-6 (Il-6), C-C motif chemokine ligand 2 (Ccl2), C-C motif chemokine ligand 7 (Ccl7), C-X-C motif chemokine ligand 1 (Cxcl1), and C-X-C motif chemokine ligand 3 (Cxcl3) and a significant decrease in the anti-inflammatory NLRP12 gene in both morphine-tolerant and placebo-control rats compared to saline-treated rats, although the changes were greater in the placebo-control animals. The Library of Integrated Network-Based Cellular Signatures’ (LINCS) connectivity map was used to analyze the list of affected genes to identify potential targets associated with the interactions of LPS and morphine tolerance. Our data indicate that, in the morphine tolerant state, the expression of NLRP12 and its related genes is altered in response to LPS and that the Vacuolar protein-sorting-associated protein 28 (VPS28), which is involved in the transport and sorting of proteins into sub-cellular vesicles, may be the key regulator of these alterations. Full article
(This article belongs to the Special Issue Advances in Neuroimmunology)
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Open AccessArticle Effect of Experimental Hand Pain on Training-Induced Changes in Motor Performance and Corticospinal Excitability
Brain Sci. 2017, 7(2), 15; doi:10.3390/brainsci7020015
Received: 9 September 2016 / Revised: 9 December 2016 / Accepted: 25 January 2017 / Published: 4 February 2017
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Abstract
Pain influences plasticity within the sensorimotor system and the aim of this study was to assess the effect of pain on changes in motor performance and corticospinal excitability during training for a novel motor task. A total of 30 subjects were allocated to
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Pain influences plasticity within the sensorimotor system and the aim of this study was to assess the effect of pain on changes in motor performance and corticospinal excitability during training for a novel motor task. A total of 30 subjects were allocated to one of two groups (Pain, NoPain) and performed ten training blocks of a visually-guided isometric pinch task. Each block consisted of 15 force sequences, and subjects modulated the force applied to a transducer in order to reach one of five target forces. Pain was induced by applying capsaicin cream to the thumb. Motor performance was assessed by a skill index that measured shifts in the speed–accuracy trade-off function. Neurophysiological measures were taken from the first dorsal interosseous using transcranial magnetic stimulation. Overall, the Pain group performed better throughout the training (p = 0.03), but both groups showed similar improvements across training blocks (p < 0.001), and there was no significant interaction. Corticospinal excitability in the NoPain group increased halfway through the training, but this was not observed in the Pain group (Time × Group interaction; p = 0.01). These results suggest that, even when pain does not negatively impact on the acquisition of a novel motor task, it can affect training-related changes in corticospinal excitability. Full article
(This article belongs to the Special Issue Motor Control and Brain Plasticity)
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Open AccessArticle Inhibitory Control under Threat: The Role of Spontaneous Eye Blinks in Post-Traumatic Stress Disorder
Brain Sci. 2017, 7(2), 16; doi:10.3390/brainsci7020016
Received: 25 July 2016 / Revised: 19 January 2017 / Accepted: 24 January 2017 / Published: 4 February 2017
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Abstract
This study is the first to explore spontaneous eye blink rate (sEBR) in individuals with post-traumatic stress disorder (PTSD). We investigated the connection between the magnitude of flanker interference in PTSD participants and sEBR during performance on a modified version of the Eriksen
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This study is the first to explore spontaneous eye blink rate (sEBR) in individuals with post-traumatic stress disorder (PTSD). We investigated the connection between the magnitude of flanker interference in PTSD participants and sEBR during performance on a modified version of the Eriksen flanker task. As a peripheral measure of cognitive control and dopaminergic function, sEBR may illuminate the relationship between PTSD and executive function. Findings revealed a positive relationship between sEBR and flanker interference in participants diagnosed with PTSD, to both threat-related and neutral stimuli, whereas this relationship was negative in participants exposed to trauma but without PTSD and in healthy controls. Although our results are suggestive of sEBR as a potential physiological index of emotional management in PTSD, most of the correlations were not significant, indicating that further research with a larger sample is needed. Full article
(This article belongs to the Special Issue The Pathogenesis of Post Traumatic Stress Disorder (PTSD))
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Open AccessArticle Spatial Impairment and Memory in Genetic Disorders: Insights from Mouse Models
Brain Sci. 2017, 7(2), 17; doi:10.3390/brainsci7020017
Received: 1 November 2016 / Revised: 15 January 2017 / Accepted: 7 February 2017 / Published: 9 February 2017
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Abstract
Research across the cognitive and brain sciences has begun to elucidate some of the processes that guide navigation and spatial memory. Boundary geometry and featural landmarks are two distinct classes of environmental cues that have dissociable neural correlates in spatial representation and follow
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Research across the cognitive and brain sciences has begun to elucidate some of the processes that guide navigation and spatial memory. Boundary geometry and featural landmarks are two distinct classes of environmental cues that have dissociable neural correlates in spatial representation and follow different patterns of learning. Consequently, spatial navigation depends both on the type of cue available and on the type of learning provided. We investigated this interaction between spatial representation and memory by administering two different tasks (working memory, reference memory) using two different environmental cues (rectangular geometry, striped landmark) in mouse models of human genetic disorders: Prader-Willi syndrome (PWScrm+/p− mice, n = 12) and Beta-catenin mutation (Thr653Lys-substituted mice, n = 12). This exploratory study provides suggestive evidence that these models exhibit different abilities and impairments in navigating by boundary geometry and featural landmarks, depending on the type of memory task administered. We discuss these data in light of the specific deficits in cognitive and brain function in these human syndromes and their animal model counterparts. Full article
(This article belongs to the Special Issue The Mechanisms of Memory in the Brain)
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Open AccessArticle Reducing Fall Risk with Combined Motor and Cognitive Training in Elderly Fallers
Brain Sci. 2017, 7(2), 19; doi:10.3390/brainsci7020019
Received: 7 November 2016 / Revised: 27 January 2017 / Accepted: 7 February 2017 / Published: 10 February 2017
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Abstract
Background. Falling is a major clinical problem in elderly people, demanding effective solutions. At present, the only effective intervention is motor training of balance and strength. Executive function-based training (EFt) might be effective at preventing falls according to evidence showing a relationship between
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Background. Falling is a major clinical problem in elderly people, demanding effective solutions. At present, the only effective intervention is motor training of balance and strength. Executive function-based training (EFt) might be effective at preventing falls according to evidence showing a relationship between executive functions and gait abnormalities. The aim was to assess the effectiveness of a motor and a cognitive treatment developed within the EU co-funded project I-DONT-FALL. Methods. In a sample of 481 elderly people at risk of falls recruited in this multicenter randomised controlled trial, the effectiveness of a motor treatment (pure motor or mixed with EFt) of 24 one-hour sessions delivered through an i-Walker with a non-motor treatment (pure EFt or control condition) was evaluated. Similarly, a 24 one-hour session cognitive treatment (pure EFt or mixed with motor training), delivered through a touch-screen computer was compared with a non-cognitive treatment (pure motor or control condition). Results. Motor treatment, particularly when mixed with EFt, reduced significantly fear of falling (F(1,478) = 6.786, p = 0.009) although to a limited extent (ES −0.25) restricted to the period after intervention. Conclusions. This study suggests the effectiveness of motor treatment empowered by EFt in reducing fear of falling. Full article
(This article belongs to the Special Issue Risk and Protective Factors for Neurocognitive Aging)
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Open AccessArticle The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline
Brain Sci. 2017, 7(2), 20; doi:10.3390/brainsci7020020
Received: 30 November 2016 / Revised: 7 February 2017 / Accepted: 8 February 2017 / Published: 15 February 2017
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Abstract
Neurodegeneration, the progressive death of neurons, loss of brain function, and cognitive decline is an increasing problem for senior populations. Its causes are poorly understood and therapies are largely ineffective. Neurons, with high energy and oxygen requirements, are especially vulnerable to detrimental factors,
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Neurodegeneration, the progressive death of neurons, loss of brain function, and cognitive decline is an increasing problem for senior populations. Its causes are poorly understood and therapies are largely ineffective. Neurons, with high energy and oxygen requirements, are especially vulnerable to detrimental factors, including age-related dysregulation of biochemical pathways caused by altered expression of multiple genes. GHK (glycyl-l-histidyl-l-lysine) is a human copper-binding peptide with biological actions that appear to counter aging-associated diseases and conditions. GHK, which declines with age, has health promoting effects on many tissues such as chondrocytes, liver cells and human fibroblasts, improves wound healing and tissue regeneration (skin, hair follicles, stomach and intestinal linings, boney tissue), increases collagen, decorin, angiogenesis, and nerve outgrowth, possesses anti-oxidant, anti-inflammatory, anti-pain and anti-anxiety effects, increases cellular stemness and the secretion of trophic factors by mesenchymal stem cells. Studies using the Broad Institute Connectivity Map show that GHK peptide modulates expression of multiple genes, resetting pathological gene expression patterns back to health. GHK has been recommended as a treatment for metastatic cancer, Chronic Obstructive Lung Disease, inflammation, acute lung injury, activating stem cells, pain, and anxiety. Here, we present GHK’s effects on gene expression relevant to the nervous system health and function. Full article
(This article belongs to the Special Issue Risk and Protective Factors for Neurocognitive Aging)
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Open AccessArticle Diffusion Assessment of Cortical Changes, Induced by Traumatic Spinal Cord Injury
Brain Sci. 2017, 7(2), 21; doi:10.3390/brainsci7020021
Received: 8 September 2016 / Revised: 14 December 2016 / Accepted: 14 February 2017 / Published: 17 February 2017
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Abstract
Promising treatments are being developed to promote functional recovery after spinal cord injury (SCI). Magnetic resonance imaging, specifically Diffusion Tensor Imaging (DTI) has been shown to non-invasively measure both axonal and myelin integrity following traumatic brain and SCI. A novel data-driven model-selection algorithm
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Promising treatments are being developed to promote functional recovery after spinal cord injury (SCI). Magnetic resonance imaging, specifically Diffusion Tensor Imaging (DTI) has been shown to non-invasively measure both axonal and myelin integrity following traumatic brain and SCI. A novel data-driven model-selection algorithm known as Diffusion Basis Spectrum Imaging (DBSI) has been proposed to more accurately delineate white matter injury. The objective of this study was to investigate whether DTI/DBSI changes that extend to level of the cerebral peduncle and internal capsule following a SCI could be correlated with clinical function. A prospective non-randomized cohort of 23 patients with chronic spinal cord injuries and 17 control subjects underwent cranial diffusion weighted imaging, followed by whole brain DTI and DBSI computations. Region-based analyses were performed on cerebral peduncle and internal capsule. Three subgroups of patients were included in the region-based analysis. Tract-Based Spatial Statistics (TBSS) was also applied to allow whole-brain white matter analysis between controls and all patients. Functional assessments were made using International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) as modified by the American Spinal Injury Association (ASIA) Scale. Whole brain white matter analysis using TBSS finds no statistical difference between controls and all patients. Only cervical ASIA A/B patients in cerebral peduncle showed differences from controls in DTI and DBSI results with region-based analysis. Cervical ASIA A/B SCI patients had higher levels of axonal injury and edema/tissue loss as measured by DBSI at the level of the cerebral peduncle. DTI Fractional Anisotropy (FA), Axial Diffusivity (AD) and Radial Diffusivity (RD) was able to detect differences in cervical ASIA A/B patients, but were non-specific to pathologies. Increased water fraction indicated by DBSI non-restricted isotropic diffusion fraction in the cerebral peduncle, explains the simultaneously increased DTI AD and DTI RD values. Our results further demonstrate the utility of DTI to detect disruption in axonal integrity in white matter, yet a clear shortcoming in differentiating true axonal injury from inflammation/tissue loss. Our results suggest a preservation of axonal integrity at the cortical level and has implications for future regenerative clinical trials. Full article
(This article belongs to the Special Issue Acute and Chronic Systemic Alterations Produced by Spinal Trauma)
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Review

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Open AccessReview Surgical Neurostimulation for Spinal Cord Injury
Brain Sci. 2017, 7(2), 18; doi:10.3390/brainsci7020018
Received: 21 December 2016 / Revised: 30 January 2017 / Accepted: 2 February 2017 / Published: 10 February 2017
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Abstract
Traumatic spinal cord injury (SCI) is a devastating neurological condition characterized by a constellation of symptoms including paralysis, paraesthesia, pain, cardiovascular, bladder, bowel and sexual dysfunction. Current treatment for SCI involves acute resuscitation, aggressive rehabilitation and symptomatic treatment for complications. Despite the progress
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Traumatic spinal cord injury (SCI) is a devastating neurological condition characterized by a constellation of symptoms including paralysis, paraesthesia, pain, cardiovascular, bladder, bowel and sexual dysfunction. Current treatment for SCI involves acute resuscitation, aggressive rehabilitation and symptomatic treatment for complications. Despite the progress in scientific understanding, regenerative therapies are lacking. In this review, we outline the current state and future potential of invasive and non-invasive neuromodulation strategies including deep brain stimulation (DBS), spinal cord stimulation (SCS), motor cortex stimulation (MCS), transcutaneous direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in the context of SCI. We consider the ability of these therapies to address pain, sensorimotor symptoms and autonomic dysregulation associated with SCI. In addition to the potential to make important contributions to SCI treatment, neuromodulation has the added ability to contribute to our understanding of spinal cord neurobiology and the pathophysiology of SCI. Full article
(This article belongs to the Special Issue Deep Brain Stimulation (DBS) Applications) Printed Edition available
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Open AccessReview Physical Activity: A Viable Way to Reduce the Risks of Mild Cognitive Impairment, Alzheimer’s Disease, and Vascular Dementia in Older Adults
Brain Sci. 2017, 7(2), 22; doi:10.3390/brainsci7020022
Received: 30 November 2016 / Revised: 23 January 2017 / Accepted: 3 February 2017 / Published: 20 February 2017
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Abstract
A recent alarming rise of neurodegenerative diseases in the developed world is one of the major medical issues affecting older adults. In this review, we provide information about the associations of physical activity (PA) with major age-related neurodegenerative diseases and syndromes, including Alzheimer’s
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A recent alarming rise of neurodegenerative diseases in the developed world is one of the major medical issues affecting older adults. In this review, we provide information about the associations of physical activity (PA) with major age-related neurodegenerative diseases and syndromes, including Alzheimer’s disease, vascular dementia, and mild cognitive impairment. We also provide evidence of PA’s role in reducing the risks of these diseases and helping to improve cognitive outcomes in older adults. Finally, we describe some potential mechanisms by which this protective effect occurs, providing guidelines for future research. Full article
(This article belongs to the Special Issue Risk and Protective Factors for Neurocognitive Aging)
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