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[PMID]: 27179221
[Au] Autor:Kobek M; Jankowski Z; Szala J; Gaszczyk-Ozarowski Z; Palasz A; Skowronek R
[Ti] Title:Time-related morphometric studies of neurofilaments in brain contusions.
[So] Source:Folia Neuropathol;54(1):50-8, 2016.
[Is] ISSN:1509-572X
[Cp] Country of publication:Poland
[La] Language:eng
[Ab] Abstract:In forensic pathology age determination of injuries is of key importance. The purpose of the study was to analyze morphometrically changes in neurofilaments following the brain contusion and relate them to the length of the time of survival. To do this, the authors analyzed specimens of brains collected during medicolegal autopsies. According to the available literature, no such study involving material from deceased humans was conducted. The researched material was divided into nine subgroups (10 cases each) according to the time of death of persons: immediately at the crime site, 12 hours, 24 hours, 2 days, 3 days, 4 days, 5 days, 6 days and 7 days after head trauma. Neurofilaments were immunohistochemically stained and evaluated quantitatively using the Met-Ilo computer application. The initial results were then analyzed statistically with the one way analysis of variance (ANOVA) and the least significant difference (LSD) tests. It was calculated that there are significant differences in numbers and area fractions of neurofilaments within 7 days after head trauma. It must be concluded that morphometric analysis of neurofilaments is a promising method but further studies are required.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Js] Journal subset:IM
[St] Status:In-Data-Review

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[PMID]: 27179219
[Au] Autor:Batista K; Costa B; Pablo I; Vega IF; Morales J; Alvarez AV; Meilán A; Astudillo A; Alvarez KY
[Ad] Address:Kelvin Manuel Piña Batista, MD, MSc, MBA, PhD, Department of Neurosurgery, Hospital Universitario Central de Asturias, Av. de Las Segadas 22, 4a 33006 Oviedo, Spain, phone: +34 693 86 24 81, e-mail: pineappledr@gmail.com.
[Ti] Title:Analysis of Olig2 and YKL-40 expression: a clinicopathological/immunohistochemical study for the distinction between subventricular zone II and III glioblastomas.
[So] Source:Folia Neuropathol;54(1):31-9, 2016.
[Is] ISSN:1509-572X
[Cp] Country of publication:Poland
[La] Language:eng
[Ab] Abstract:Glioblastomas (GBs) are the most common and lethal primary brain tumors in the adults. Glioblastomas originates either from astrocytes that have accumulated mutations and de-differentiated or from neural stem cells within the subventricular zone (SVZ) in close contact with the vasculature. Recently, several studies have hypothesized that gliomagenesis occurs in perivascular niches with highly invasive peripheral proliferating zones. The purpose of our study was to investigate the pathological and clinical significance of Olig2 and YKL40 immunoexpression in 152 GBs in relationship to the SVZ II and III. Olig2 expressions were successfully detected in 12 (15.58%) of 77 SVZ type II GBs and 16 (21.3%) of 75 SVZ type III GBs, respectively. YKL-40 expression was observed in 45 (58.4%) of 77 SVZ type II GBs and in 17 (22.6%) of 75 SVZ type III GBs, respectively. Stepwise multivariate Cox proportional hazards models were used, and the prognostic factors to significantly impact OS were: PFS < 54 weeks (HR: 5.86; CI: 3.02-11.33; p = 0.00); radiotherapy (HR: 0.34; CI: 0.18-0.60; p = 0.00); radio- and chemotherapy (HR: 0.05; CI: 0.03-0.10; p = 0.0), and YKL-40+ GBs (HR: 1.61; CI: 1.28-2.31; p = 0.01).
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Js] Journal subset:IM
[St] Status:In-Data-Review

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[PMID]: 27179217
[Au] Autor:Szalardy L; Molnar M; Torok R; Zadori D; Vecsei L; Klivenyi P; Liberski P; Kovacs GG
[Ti] Title:Histopathological comparison of Kearns-Sayre syndrome and PGC-1α-deficient mice suggests a novel concept for vacuole formation in mitochondrial encephalopathy.
[So] Source:Folia Neuropathol;54(1):9-22, 2016.
[Is] ISSN:1509-572X
[Cp] Country of publication:Poland
[La] Language:eng
[Ab] Abstract:Despite the current hypotheses about myelinic and astrocytic ion-dyshomeostasis underlying white (WM) and grey matter (GM) vacuolation in mitochondrial encephalopathies, there is a paucity of data on the exact mechanism of vacuole formation. To revisit the concepts of vacuole formation associated with mitochondrial dysfunction, we performed a comparative neuropathological analysis in Kearns-Sayre syndrome (KSS) and full-length peroxisome proliferator-activated receptor-g coactivator-1a (FL-PGC-1a)-deficient mice, a recently proposed morphological model of mitochondrial encephalopathies. Brain tissues from an individual with genetically proven KSS (22-year-old man) and aged FL-PGC-1a-deficient and wild-type (male, 70-75-week-old) mice were analysed using ultrastructural and immunohistochemical methods, with a specific focus on myelin-related, oligodendroglial, axonal and astrocytic pathologies. Besides demonstrating remarkable similarities in the lesion profile of KSS and FL-PGC-1a-deficient mice, this study first provides morphological evidence for the identical origin of WM and GM vacuolation as well as for the presence of intracytoplasmic oligodendroglial vacuoles in mitochondriopathies. Based on these observations, the paper proposes a theoretical model for the development of focal myelin vacuolation as opposed to the original concepts of intramyelin oedema. Placing oligodendrocytes in the centre of tissue lesioning in conditions related to defects in mitochondria, our observations support the rationale for cytoprotective targeting of oligodendrocytes in mitochondrial encephalopathies, and may also have implications in brain aging and multiple sclerosis, as discussed.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Js] Journal subset:IM
[St] Status:In-Data-Review

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[PMID]: 27179170
[Au] Autor:Mehregan H; Najmabadi H; Kahrizi K
[Ad] Address:Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Evin, Tehran 19834, Iran.
[Ti] Title:Genetic Studies in Intellectual Disability and Behavioral Impairment.
[So] Source:Arch Iran Med;19(5):363-75, 2016 May.
[Is] ISSN:1735-3947
[Cp] Country of publication:Iran
[La] Language:eng
[Ab] Abstract: Intellectual Disability (ID, also known as mental retardation) is a debilitating neurodevelopmental disorder affecting nearly 1% of the general population worldwide. Occurrence of behavioral disorders in individuals with ID is four times higher than that in the general population. An increasing number of studies seek to find a common pathway to elucidate brain structure/function and its contribution to behavior. This article deals with different behavioral disorders reported in individuals with syndromic and non-syndromic ID and possible candidate genes, most of which are involved in synaptic formation and function. Many ID cases with behavior impairments were referred to genetic centers to identify genetic causes; Therefore, the authors gathered data from their own studies along with similar published reports, to provide a review on genes involved in brain development and cognition. In this study, we argued how defects in genes with diverse functional role may contribute to  behavior impairments and a brain malfunction.  Evidences from individual with cognitive impairment as well as murine and drosophila animal models have been used to show  behavioral consequences of functional deficits in genes speculated to play a role in cognition and learning.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:0161905/AIM.0012

  5 / 1346584 MEDLINE  
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[PMID]: 26631648
[Au] Autor:Lin M; Lachman HM; Zheng D
[Ad] Address:Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY, USA.
[Ti] Title:Transcriptomics analysis of iPSC-derived neurons and modeling of neuropsychiatric disorders.
[So] Source:Mol Cell Neurosci;73:32-42, 2016 Jun.
[Is] ISSN:1095-9327
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Induced pluripotent stem cell (iPSC)-derived neurons and neural progenitors are great resources for studying neural development and differentiation and their disruptions in disease conditions, and hold the promise of future cell therapy. In general, iPSC lines can be established either specifically from patients with neuropsychiatric disorders or from healthy subjects. The iPSCs can then be induced to differentiate into neural lineages and the iPSC-derived neurons are valuable for various types of cell-based assays that seek to understand disease mechanisms and identify and test novel therapies. In addition, it is an ideal system for gene expression profiling (i.e., transcriptomic analysis), an efficient and cost-effective way to explore the genetic programs regulating neurodevelopment. Moreover, transcriptomic comparison, which can be performed between patient-derived samples and controls, or in control lines in which the expression of specific genes has been disrupted, can uncover convergent gene targets and pathways that are downstream of the hundreds of candidate genes that have been associated with neuropsychiatric disorders. The results, especially after integration with spatiotemporal transcriptomic profiles of normal human brain development, have indeed helped to uncover gene networks, molecular pathways, and cellular signaling that likely play critical roles in disease development and progression. On the other hand, despite the great promise, many challenges remain in the usage of iPSC-derived neurons for modeling neuropsychiatric disorders, for example, how to generate relatively homogenous populations of specific neuronal subtypes that are affected in a particular disorder and how to better address the genetic heterogeneity that exists in the patient population.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review

  6 / 1346584 MEDLINE  
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[PMID]: 27149650
[Au] Autor:Zwingenberger AL; Pollard RE; Taylor SL; Chen RX; Nunley J; Kent MS
[Ad] Address:Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA....
[Ti] Title:Perfusion and Volume Response of Canine Brain Tumors to Stereotactic Radiosurgery and Radiotherapy.
[So] Source:J Vet Intern Med;30(3):827-35, 2016 May.
[Is] ISSN:1939-1676
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) are highly conformal, high-dose radiation treatment techniques used to treat people and dogs with brain tumors. OBJECTIVES: To evaluate the response to SRS- and SRT-treated tumors using volume and perfusion variables and to measure the survival times of affected dogs. ANIMALS: Prospective study of 34 dogs with evidence of brain tumors undergoing stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). METHODS: Computed tomography and MRI imaging were used to calculate tumor volume and perfusion at baseline, and at 3 months and 6 months after treatment. Survival analysis was performed to evaluate treatment efficacy. RESULTS: Mean tumor volume significantly declined from baseline to the first recheck by -0.826 cm(3) (95% CI: -1.165, -0.487) (P < .001); this reduction was maintained at the second recheck. Blood flow and blood volume declined significantly in the tumor after treatment. Median survival was 324 days (95% CI: 292.8, 419.4), and 4 dogs survived longer than 650 days. Neither actual tumor volume (hazard ratio = 1.21, P = .19) nor the change in tumor volume from the baseline (hazard ratio = 1.38, P = .12) significantly affected the hazard of death because of the tumor. CONCLUSIONS AND CLINICAL IMPORTANCE: Stereotactic radiosurgery and SRT are effective treatments for reducing tumor volume, blood flow, and blood volume. Treated dogs surviving for more than 1 year are more likely to die from other causes than of their primary brain tumor. SRS and SRT should be considered for noninvasive treatment of intracranial brain tumors.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1111/jvim.13945

  7 / 1346584 MEDLINE  
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[PMID]: 26414451
[Au] Autor:Mabray MC; Talbott JF; Whetstone WD; Dhall SS; Phillips DB; Pan JZ; Manley GT; Bresnahan JC; Beattie MS; Haefeli J; Ferguson AR
[Ad] Address:1 Department of Radiology and Biomedical Imaging, University of California San Francisco and San Francisco General Hospital , San Francisco, California....
[Ti] Title:Multidimensional Analysis of Magnetic Resonance Imaging Predicts Early Impairment in Thoracic and Thoracolumbar Spinal Cord Injury.
[So] Source:J Neurotrauma;33(10):954-62, 2016 May 15.
[Is] ISSN:1557-9042
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Literature examining magnetic resonance imaging (MRI) in acute spinal cord injury (SCI) has focused on cervical SCI. Reproducible systems have been developed for MRI-based grading; however, it is unclear how they apply to thoracic SCI. Our hypothesis is that MRI measures will group as coherent multivariate principal component (PC) ensembles, and that distinct PCs and individual variables will show discriminant validity for predicting early impairment in thoracic SCI. We undertook a retrospective cohort study of 25 patients with acute thoracic SCI who underwent MRI on admission and had American Spinal Injury Association Impairment Scale (AIS) assessment at hospital discharge. Imaging variables of axial grade, sagittal grade, length of injury, thoracolumbar injury classification system (TLICS), maximum canal compromise (MCC), and maximum spinal cord compression (MSCC) were collected. We performed an analytical workflow to detect multivariate PC patterns followed by explicit hypothesis testing to predict AIS at discharge. All imaging variables loaded positively on PC1 (64.3% of variance), which was highly related to AIS at discharge. MCC, MSCC, and TLICS also loaded positively on PC2 (22.7% of variance), while variables concerning cord signal abnormality loaded negatively on PC2. PC2 was highly related to the patient undergoing surgical decompression. Variables of signal abnormality were all negatively correlated with AIS at discharge with the highest level of correlation for axial grade as assessed with the Brain and Spinal Injury Center (BASIC) score. A multiple variable model identified BASIC as the only statistically significant predictor of AIS at discharge, signifying that BASIC best captured the variance in AIS within our study population. Our study provides evidence of convergent validity, construct validity, and clinical predictive validity for the sampled MRI measures of SCI when applied in acute thoracic and thoracolumbar SCI.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1089/neu.2015.4093

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[PMID]: 26746186
[Au] Autor:Müller HP; Turner MR; Grosskreutz J; Abrahams S; Bede P; Govind V; Prudlo J; Ludolph AC; Filippi M; Kassubek J; Neuroimaging Society in ALS (NiSALS) DTI Study Group
[Ad] Address:Department of Neurology, University of Ulm, Ulm, Germany....
[Ti] Title:A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis.
[So] Source:J Neurol Neurosurg Psychiatry;87(6):570-9, 2016 Jun.
[Is] ISSN:1468-330X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVE: Damage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across multiple MRI scanners and patient cohorts. A multicentre study was undertaken to assess structural connectivity in ALS within a large sample size. METHODS: 442 DTI data sets from patients with ALS (N=253) and controls (N=189) were collected for this retrospective study, from eight international ALS-specialist clinic sites. Equipment and DTI protocols varied across the centres. Fractional anisotropy (FA) maps of the control participants were used to establish correction matrices to pool data, and correction algorithms were applied to the FA maps of the control and ALS patient groups. RESULTS: Analysis of data pooled from all centres, using whole-brain-based statistical analysis of FA maps, confirmed the most significant alterations in the corticospinal tracts, and captured additional significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions of the ALS group that coincided with postmortem neuropathological stages. Stratification of the ALS group for disease severity (ALS functional rating scale) confirmed these findings. INTERPRETATION: This large-scale study overcomes the challenges associated with processing and analysis of multiplatform, multicentre DTI data, and effectively demonstrates the anatomical fingerprint patterns of changes in a DTI metric that reflect distinct ALS disease stages. This success paves the way for the use of DTI-based metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1136/jnnp-2015-311952

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[PMID]: 26733601
[Au] Autor:Menke RA; Proudfoot M; Wuu J; Andersen PM; Talbot K; Benatar M; Turner MR
[Ad] Address:Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK FMRIB Centre, John Radcliffe Hospital, University of Oxford, Oxford, UK....
[Ti] Title:Increased functional connectivity common to symptomatic amyotrophic lateral sclerosis and those at genetic risk.
[So] Source:J Neurol Neurosurg Psychiatry;87(6):580-8, 2016 Jun.
[Is] ISSN:1468-330X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To discern presymptomatic changes in brain structure or function using advanced MRI in carriers of mutations predisposing to amyotrophic lateral sclerosis (ALS). METHODS: T1-weighted, diffusion weighted and resting state functional MRI data were acquired at 3 T for 12 asymptomatic mutation carriers (psALS), 12 age-matched controls and affected patients with ALS. Cortical thickness analysis, voxel-based morphometry, volumetric and shape analyses of subcortical structures, tract-based spatial statistics of metrics derived from the diffusion tensor, and resting state functional connectivity (FC) analyses were performed. RESULTS: Grey matter cortical thickness and shape analysis revealed significant atrophy in patients with ALS (but not psALS) compared with controls in the right primary motor cortex and right caudate. Comparison of diffusion tensor metrics showed widespread fractional anisotropy and radial diffusivity differences in patients with ALS compared to controls and the psALS group, encompassing parts of the corpus callosum, corticospinal tracts and superior longitudinal fasciculus. While FC in the resting-state sensorimotor network was similar in psALS and controls, FC between the cerebellum and a network comprising the precuneus, cingulate & middle frontal lobe was significantly higher in psALS and affected ALS compared to controls. CONCLUSIONS: Rather than structural brain changes, increased FC may be among the earliest detectable brain abnormalities in asymptomatic carriers of ALS-causing gene mutations. With replication and significant refinement, this technique has potential in the future assessment of neuroprotective strategies.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1136/jnnp-2015-311945

  10 / 1346584 MEDLINE  
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[PMID]: 26967228
[Au] Autor:Silbert LC; Dodge HH; Lahna D; Promjunyakul NO; Austin D; Mattek N; Erten-Lyons D; Kaye JA
[Ad] Address:NIA-Layton Aging & Alzheimer's Disease Center, Department of Neurology, Oregon Health & Science University, Portland, OR, USA....
[Ti] Title:Less Daily Computer Use is Related to Smaller Hippocampal Volumes in Cognitively Intact Elderly.
[So] Source:J Alzheimers Dis;52(2):713-7, 2016 Mar 9.
[Is] ISSN:1875-8908
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND: Computer use is becoming a common activity in the daily life of older individuals and declines over time in those with mild cognitive impairment (MCI). The relationship between daily computer use (DCU) and imaging markers of neurodegeneration is unknown. OBJECTIVE: The objective of this study was to examine the relationship between average DCU and volumetric markers of neurodegeneration on brain MRI. METHODS: Cognitively intact volunteers enrolled in the Intelligent Systems for Assessing Aging Change study underwent MRI. Total in-home computer use per day was calculated using mouse movement detection and averaged over a one-month period surrounding the MRI. Spearman's rank order correlation (univariate analysis) and linear regression models (multivariate analysis) examined hippocampal, gray matter (GM), white matter hyperintensity (WMH), and ventricular cerebral spinal fluid (vCSF) volumes in relation to DCU. A voxel-based morphometry analysis identified relationships between regional GM density and DCU. RESULTS: Twenty-seven cognitively intact participants used their computer for 51.3 minutes per day on average. Less DCU was associated with smaller hippocampal volumes (r = 0.48, p = 0.01), but not total GM, WMH, or vCSF volumes. After adjusting for age, education, and gender, less DCU remained associated with smaller hippocampal volume (p = 0.01). Voxel-wise analysis demonstrated that less daily computer use was associated with decreased GM density in the bilateral hippocampi and temporal lobes. CONCLUSIONS: Less daily computer use is associated with smaller brain volume in regions that are integral to memory function and known to be involved early with Alzheimer's pathology and conversion to dementia. Continuous monitoring of daily computer use may detect signs of preclinical neurodegeneration in older individuals at risk for dementia.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3233/JAD-160079


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