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    1839 results match your criteria Brain Pathology[Journal]

    1 OF 37

    BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions are frequent in epithelioid glioblastomas: A histological and molecular analysis focusing on intratumoral heterogeneity.
    Brain Pathol 2017 Nov 4. Epub 2017 Nov 4.
    Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Japan.
    Epithelioid glioblastoma (E-GBM) is a rare aggressive variant of IDH-wildtype glioblastoma newly recognized in the 2016 World Health Organization classification, composed predominantly of monotonous, patternless sheets of round cells with laterally positioned nuclei and plump eosinophilic cytoplasm. Approximately 50% of E-GBM harbor BRAF V600E, which is much less frequently found in other types of glioblastomas. Most E-GBM are recognized as primary/de novo lesions; however, several E-GBM with co- or pre-existing lower-grade lesions have been reported. Read More

    OXIDATIVE STRESS AND MITOCHONDRIAL DYNAMICS MALFUNCTION ARE LINKED IN PELIZAEUS-MERZBACHER DISEASE.
    Brain Pathol 2017 Oct 13. Epub 2017 Oct 13.
    Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
    Pelizaeus-Merzbacher disease (PMD) is a fatal hypomyelinating disorder characterized by early impairment of motor development, nystagmus, choreoathetotic movements, ataxia and progressive spasticity. PMD is caused by variations in the proteolipid protein gene PLP1, which encodes the two major myelin proteins of the central nervous system, PLP and its spliced isoform DM20, in oligodendrocytes. Large duplications including the entire PLP1 gene are the most frequent causative mutation leading to the classical form of PMD. Read More

    DOWNREGULATED APOPTOSIS AND AUTOPHAGY AFTER ANTI-Aβ IMMUNOTHERAPY IN ALZHEIMER'S DISEASE.
    Brain Pathol 2017 Oct 13. Epub 2017 Oct 13.
    Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
    Aβ immunisation of Alzheimer's disease (AD) patients in the AN1792 (Elan Pharmaceuticals) trial caused Aβ removal and a decreased density of neurons in the cerebral cortex. As preservation of neurons may be a critical determinant of outcome after Aβ immunisation, we have assessed the impact of previous Aβ immunisation on the expression of a range of apoptotic proteins in post-mortem human brain tissue. Cortex from 13 AD patients immunised with AN1792 (iAD) and from 27 non-immunised AD (cAD) cases was immunolabelled for pro-apoptotic proteins implicated in AD pathophysiology: phosphorylated c-Jun N-terminal kinase (pJNK), activated caspase3 (a-casp3), phosphorylated GSK3β on tyrosine 216 (GSK3βtyr216 ), p53 and Cdk5/p35. Read More

    Astroblastoma: a distinct tumor entity characterized by alterations of the X chromosome and MN1 rearrangement.
    Brain Pathol 2017 Oct 9. Epub 2017 Oct 9.
    Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Japan.
    Astroblastoma is a rare, enigmatic tumor of the central nervous system (CNS) which shares some clinicopathologic aspects with other CNS tumors, especially ependymoma. To further clarify the nature of astroblastoma, we performed clinicopathologic and molecular genetic studies on eight cases of astroblastoma. The median age of the patients was 14. Read More

    Epithelioid glioblastomas stratify into established diagnostic subsets upon integrated molecular analysis.
    Brain Pathol 2017 Oct 9. Epub 2017 Oct 9.
    Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
    Epithelioid glioblastoma (eGBM) is a newly defined and rare GBM variant in the current WHO 2016 classification. BRAF V600E mutation is overrepresented in these tumors and there is known some morphological overlap with anaplastic epithelioid PXA (ePXA). In order to further elucidate this diagnostic category, we molecularly characterized 64 pediatric and adult examples initially diagnosed as "eGBM. Read More

    TREM2 expression in the human brain: a marker of monocyte recruitment?
    Brain Pathol 2017 Oct 7. Epub 2017 Oct 7.
    Clinical Neurosciences, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, UK.
    Mutation in the triggering receptor expressed on myeloid cells (TREM) 2 gene has been identified as a risk factor for several neurodegenerative diseases including Alzheimer's disease (AD). Experimental studies using animal models of AD have highlighted a number of functions associated with TREM2 and its expression by microglial cells. It has therefore been assumed that this is also the case in humans. Read More

    Diffuse gliomas with FGFR3-TACC3 fusion have characteristic histopathological and molecular features.
    Brain Pathol 2017 Oct 4. Epub 2017 Oct 4.
    AP-HP, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Service de Neuropathologie Raymond Escourolle, Paris, France.
    Adult glioblastomas, IDH-wildtype represent a heterogeneous group of diseases. They are resistant to conventional treatment by concomitant radiochemotherapy and carry a dismal prognosis. The discovery of oncogenic gene fusions in these tumors has led to prospective targeted treatments, but identification of these rare alterations in practice is challenging. Read More

    Multimodal molecular analysis of astroblastoma enables reclassification of most cases into more specific molecular entities.
    Brain Pathol 2017 Sep 28. Epub 2017 Sep 28.
    Department of Pathology, Division of Neuropathology, University of California, San Francisco, CA.
    Astroblastoma is a rare and controversial glioma with variable clinical behavior. The diagnosis currently rests on histologic findings of a circumscribed glioma with astroblastomatous pseudorosettes and vascular hyalinization. Immunohistochemical studies have suggested different oncogenic drivers, such as BRAF p. Read More

    Spinal Lewy body pathology in older adults without an antemortem diagnosis of Parkinson's disease.
    Brain Pathol 2017 Sep 28. Epub 2017 Sep 28.
    Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL.
    To test the hypothesis that Lewy body pathology (LBs) is present in the spinal cord of older community-dwelling adults without a clinical diagnosis of Parkinson's disease (PD). We studied 162 prospective autopsies from older adults with PD (N = 6) and without PD (N = 156). We documented the presence of LBs in cerebrum and brainstem structures from each of the six regions used for Braak PD staging and four spinal cord levels (C5/6, T7, L4/5 and S4/5). Read More

    Neuronal Rho GTPase Rac1 elimination confers neuroprotection in a mouse model of permanent ischemic stroke.
    Brain Pathol 2017 Sep 28. Epub 2017 Sep 28.
    i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
    The Rho GTPase Rac1 is a multifunctional protein involved in distinct pathways ranging from development to pathology. The aim of the present study was to unravel the contribution of neuronal Rac1 in regulating the response to brain injury induced by permanent focal cerebral ischemia (pMCAO). Our results show that pMCAO significantly increased total Rac1 levels in wild type mice, mainly through rising nuclear Rac1, while a reduction in Rac1 activation was observed. Read More

    Fetal microchimerism in human brain tumors.
    Brain Pathol 2017 Sep 18. Epub 2017 Sep 18.
    Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
    Sex differences in cancer incidence and survival, including central nervous system tumors, are well documented. Multiple mechanisms contribute to sex differences in health and disease. Recently, the presence of fetal-in-maternal microchimeric cells has been shown to have prognostic significance in breast and colorectal cancers. Read More

    Hippocampal sclerosis, hippocampal neuron loss patterns and Tdp-43 in the aged population.
    Brain Pathol 2017 Aug 18. Epub 2017 Aug 18.
    Institute of Public Health, University of Cambridge, Cambridge, UK.
    Hippocampal neuron loss is a common neuropathological feature in old age with various underlying etiologies. Hippocampal sclerosis of aging (HS-Aging) is neuropathologically characterized by severe CA1 neuronal loss and frequent presence of transactive response DNA-binding protein of 43 kDa (TDP-43) aggregations. Its etiology is unclear and currently no standardized approaches to measure HS-Aging exist. Read More

    Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?
    Brain Pathol 2017 Aug 19. Epub 2017 Aug 19.
    Department of (Neuro)Pathology, Academic Medical Center, Amsterdam, The Netherlands.
    Multinodular and vacuolating neuronal tumor (MVNT) is a new pattern of neuronal tumour included in the recently revised WHO 2016 classification of tumors of the CNS. There are 15 reports in the literature to date. They are typically associated with late onset epilepsy and a neoplastic vs. Read More

    Protein astrogliopathies in human neurodegenerative diseases and aging.
    Brain Pathol 2017 Sep;27(5):675-690
    Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology and Laboratory Medicine of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
    Neurodegenerative diseases are characterized by progressive dysfunction and loss of neurons associated with depositions of pathologically altered proteins showing hierarchical involvement of brain regions. The role of astrocytes in the pathogenesis of neurodegenerative diseases is explored as contributors to neuronal degeneration or neuroprotection pathways, and also as potential mediators of the transcellular spreading of disease-associated proteins. Protein astrogliopathy (PAG), including deposition of amyloid-β, prion protein, tau, α-synuclein, and very rarely transactive response DNA-binding protein 43 (TDP-43) is not unprecedented or unusual in neurodegenerative diseases. Read More

    Stratification of astrocytes in healthy and diseased brain.
    Brain Pathol 2017 Sep;27(5):629-644
    Department of Neurobiology, Civitan International Research Center and Center for Glial Biology in Medicine, Evelyn F. McKnight Brain Institute, Atomic Force Microscopy & Nanotechnology Laboratories, 1719 6th Avenue South, CIRC 429, University of Alabama at Birmingham, Birmingham, AL 35294-0021.
    Astrocytes, a subtype of glial cells, come in variety of forms and functions. However, overarching role of these cell is in the homeostasis of the brain, be that regulation of ions, neurotransmitters, metabolism or neuronal synaptic networks. Loss of homeostasis represents the underlying cause of all brain disorders. Read More

    Diversity of astroglial responses across human neurodegenerative disorders and brain aging.
    Brain Pathol 2017 Sep;27(5):645-674
    Department of Pathology and Experimental Therapeutics, University of Barcelona, Barcelona, Spain.
    Astrogliopathy refers to alterations of astrocytes occurring in diseases of the nervous system, and it implies the involvement of astrocytes as key elements in the pathogenesis and pathology of diseases and injuries of the central nervous system. Reactive astrocytosis refers to the response of astrocytes to different insults to the nervous system, whereas astrocytopathy indicates hypertrophy, atrophy/degeneration and loss of function and pathological remodeling occurring as a primary cause of a disease or as a factor contributing to the development and progression of a particular disease. Reactive astrocytosis secondary to neuron loss and astrocytopathy due to intrinsic alterations of astrocytes occur in neurodegenerative diseases, overlap each other, and, together with astrocyte senescence, contribute to disease-specific astrogliopathy in aging and neurodegenerative diseases with abnormal protein aggregates in old age. Read More

    Alterations in the steroid biosynthetic pathways in the human prefrontal cortex in mood disorders: A post-mortem study.
    Brain Pathol 2017 Jul 27. Epub 2017 Jul 27.
    Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands.
    Altered levels of steroids have been reported in the brain, cerebral spinal fluid and plasma of patients with mood disorders. Neuroimaging studies have reported both functional and structural alterations in mood disorders, for instance in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC). In order to determine whether the endogenous production of steroids is altered in the ACC and DLPFC of patients with major depressive disorder (MDD) or bipolar disorder (BPD), quantitative real-time PCR was performed to detect mRNA expression level of key enzymes in the steroid biosynthetic pathways. Read More

    Tissue microarray methodology identifies complement pathway activation and dysregulation in progressive multiple sclerosis.
    Brain Pathol 2017 Jul 14. Epub 2017 Jul 14.
    Division of Infection and Immunity, Henry Wellcome Building, Cardiff University, Cardiff, CF14 4XW, United Kingdom.
    The complement pathway has potential contributions to both white (WM) and grey matter (GM) pathology in Multiple Sclerosis (MS). A quantitative assessment of complement involvement is lacking. Here we describe the use of Tissue MicroArray (TMA) methodology in conjunction with immunohistochemistry to investigate the localization of complement pathway proteins in progressive MS cortical GM and subcortical WM. Read More

    Autophagy in neurodegenerative diseases: pathogenesis and therapy.
    Brain Pathol 2017 Jul 13. Epub 2017 Jul 13.
    The Key Laboratory of Stem Cell Biology and Neurogenomic Laboratory, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
    The most prevalent pathological features of many neurodegenerative diseases are the aggregation of misfolded proteins and the loss of certain neuronal populations. Autophagy, as major intracellular machinery for degrading aggregated proteins and damaged organelles, has been reported to be involved in the occurrence of pathological changes in many neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. In this review, we summarize most recent research progress in this topic and provide a new perspective regarding autophagy regulation on the pathogenesis of neurodegenerative diseases. Read More

    Understanding neurodevelopmental disorders using human pluripotent stem cell-derived neurons.
    Brain Pathol 2017 Jul;27(4):508-517
    Neuroscience and Mental Health Research Institute, School of Medicine and School of Biosciences, Cardiff University, Cardiff, United Kingdom.
    Research into psychiatric disorders has long been hindered by the lack of appropriate models. Induced pluripotent stem cells (iPSCs) offer an unlimited source of patient-specific cells, which in principle can be differentiated into all disease-relevant somatic cell types to create in vitro models of the disorder of interest. Here, neuronal differentiation protocols available for this purpose and the current progress on iPSCs-based models of schizophrenia, autism spectrum disorders and bipolar disorder were reviewed. Read More

    Modeling the C9ORF72 repeat expansion mutation using human induced pluripotent stem cells.
    Brain Pathol 2017 Jul;27(4):518-524
    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, EH16 4UU, UK.
    C9ORF72 repeat expansion is the most frequent causal genetic mutation giving rise to amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD). The relatively recent discovery of the C9ORF72 repeat expansion in 2011 and the complexity of the mutation have meant that animal models that successfully recapitulate human C9ORF72 repeat expansion-mediated disease are only now emerging. Concurrent advances in the use of patient-derived induced pluripotent stem cells (iPSCs) to model aspects of neurological disease offers an additional approach for the study of C9ORF72 mutation. Read More

    Modeling tau pathology in human stem cell derived neurons.
    Brain Pathol 2017 Jul;27(4):525-529
    Department of Molecular Neuroscience, UCL Institute of Neurology, London, WC1N 1PJ, UK.
    Tau pathology is a defining characteristic of multiple neurodegenerative disorders including Alzheimer's disease (AD) and Frontotemporal Dementia (FTD) with tau pathology. There is strong evidence from genetics and experimental models to support a central role for tau dysfunction in neuronal death, suggesting tau is a promising therapeutic target for AD and FTD. However, the development of tau pathology can precede symptom onset by several years, so understanding the earliest molecular events in tauopathy is a priority area of research. Read More

    Modeling Parkinson's disease with induced pluripotent stem cells harboring α-synuclein mutations.
    Brain Pathol 2017 Jul;27(4):545-551
    MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, The University of Edinburgh, Edinburgh, EH16 4UU, UK.
    Parkinson's disease (PD) is a common neurodegenerative condition affecting more than 8 million people worldwide. Although, the majority of PD cases are sporadic in nature, there are a growing number of monogenic mutations identified to cause PD in a highly penetrant manner. Many of these familial mutations give rise to a condition that is clinically and neuropathologically similar, if not identical, to sporadic PD. Read More

    Astrocytes in a dish: Using pluripotent stem cells to model neurodegenerative and neurodevelopmental disorders.
    Brain Pathol 2017 Jul;27(4):530-544
    Trinity College Institute for Neuroscience, Trinity College Dublin 2, Ireland.
    Neuroscience and Neurobiology have historically been neuron biased, yet up to 40% of the cells in the brain are astrocytes. These cells are heterogeneous and regionally diverse but universally essential for brain homeostasis. Astrocytes regulate synaptic transmission as part of the tripartite synapse, provide metabolic and neurotrophic support, recycle neurotransmitters, modulate blood flow and brain blood barrier permeability and are implicated in the mechanisms of neurodegeneration. Read More

    TGFβ pathway deregulation and abnormal phospho-SMAD2/3 staining in hereditary cerebral hemorrhage with amyloidosis-Dutch type.
    Brain Pathol 2017 May 29. Epub 2017 May 29.
    Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
    Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) is an early onset hereditary form of cerebral amyloid angiopathy (CAA) pathology, caused by the E22Q mutation in the amyloid β (Aβ) peptide. Transforming growth factor β1 (TGFβ1) is a key player in vascular fibrosis and in the formation of angiopathic vessels in transgenic mice. Therefore, we investigated whether the TGFβ pathway is involved in HCHWA-D pathogenesis in human postmortem brain tissue from frontal and occipital lobes. Read More

    Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury.
    Brain Pathol 2017 May 29. Epub 2017 May 29.
    Department of Neuroscience, Section of Neurosurgery, Uppsala University, Uppsala, Sweden.
    Deposition of amyloid-β (Aβ) is central to Alzheimer's disease (AD) pathogenesis and associated with progressive neurodegeneration in traumatic brain injury (TBI). We analyzed predisposing factors for Aβ deposition including monomeric Aβ40, Aβ42 and Aβ oligomers/protofibrils, Aβ species with pronounced neurotoxic properties, following human TBI. Highly selective ELISAs were used to analyze N-terminally intact and truncated Aβ40 and Aβ42, as well as Aβ oligomers/protofibrils, in human brain tissue, surgically resected from severe TBI patients (n = 12; mean age 49. Read More

    Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma.
    Brain Pathol 2017 May 8. Epub 2017 May 8.
    Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK.
    To assess the clinical relevance of transgenic and patient-derived xenograft models of adamantinomatous craniopharyngioma (ACP) using serial magnetic resonance imaging (MRI) and high resolution post-mortem microcomputed tomography (μ-CT), with correlation with histology and human ACP imaging. The growth patterns and radiological features of tumors arising in Hesx1(Cre/+) ;Ctnnb1(lox(ex3)/+) transgenic mice, and of patient-derived ACP xenografts implanted in the cerebral cortex, were monitored longitudinally in vivo with anatomical and functional MRI, and by ex vivo μ-CT at study end. Pathological correlates with hematoxylin and eosin stained sections were investigated. Read More

    Loss of SMARCE1 expression is a specific diagnostic marker of clear cell meningioma: a comprehensive immunophenotypical and molecular analysis.
    Brain Pathol 2017 May 5. Epub 2017 May 5.
    Department of Neuropathology, Sainte-Anne Hospital, 75014, Paris, France.
    Clear cell meningioma (CCM) is a rare grade II histopathological subtype that usually occurs in young patients and displays high recurrence rate. Germline SMARCE1 mutations have been described in hereditary forms of this disease and more recently in small syndromic and sporadic CCM series. The diagnostic value of SMARCE1 in distinguishing between CCM and other meningioma variants has not been yet established. Read More

    Pericyte-derived bone morphogenetic protein 4 underlies white matter damage after chronic hypoperfusion.
    Brain Pathol 2017 May 4. Epub 2017 May 4.
    Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
    Subcortical small vessel disease (SVD) is characterized by white matter damage resulting from arteriolosclerosis and chronic hypoperfusion. Transforming growth factor beta 1 (TGFB1) is dysregulated in the hereditary SVD, CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy). However, very little is known about the role of the largest group in the TGFB superfamily - the bone morphogenetic proteins (BMPs) - in SVD pathogenesis. Read More

    Cytotoxic CD8(+) T cell ablation enhances the capacity of regulatory T cells to delay viral elimination in Theiler's murine encephalomyelitis.
    Brain Pathol 2017 Apr 27. Epub 2017 Apr 27.
    Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
    Theiler's murine encephalomyelitis (TME) of susceptible mouse strains is a commonly used infectious animal model for multiple sclerosis. The study aim was to test the hypothesis whether cytotoxic T cell responses account for the limited impact of regulatory T cells on antiviral immunity in TME virus-induced demyelinating disease (TMEV-IDD) resistant C57BL/6 mice. TME virus-infected C57BL/6 mice were treated with (i) interleukin-2/-anti-interleukin-2-antibody-complexes to expand regulatory T cells ("Treg-expansion"), (ii) anti-CD8-antibodies to deplete cytotoxic T cells ("CD8-depletion") or (iii) with a combination of Treg-expansion and CD8-depletion ("combined treatment") prior to infection. Read More

    Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology.
    Brain Pathol 2017 May;27(3):364-369
    Developmental Biology and Cancer, UCL Great Ormond Street Institute of Child Health, University College London, Guilford Street, London, WC1N 1EH, UK.
    Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar region in childhood. Two genetically engineered mouse models have been developed and are giving valuable insights into ACP biology. These models have identified novel pathways activated in tumors, revealed an important function of paracrine signalling and extended conventional theories about the role of organ-specific stem cells in tumorigenesis. Read More

    Proteomics in pediatric cystic craniopharyngioma.
    Brain Pathol 2017 May;27(3):370-376
    Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, Rome, Italy.
    Adamantinomatous craniopharyngioma (ACP) is still often burdened by a poor prognosis in children as far as the risk of recurrence and the quality of life are concerned. Therefore, many efforts are now dedicated to investigate the molecular characteristics of this tumor aiming at finding new therapeutic options. ACP is prevalently a cystic lesion so that an increasing number of researches are focused on the analysis of its cystic content. Read More

    Models of human adamantinomatous craniopharyngioma tissue: Steps toward an effective adjuvant treatment.
    Brain Pathol 2017 May;27(3):358-363
    Institute of Pathology, Sozialstiftung Bamberg, Buger Str. 80, Bamberg, 96049, Germany.
    Even though ACP is a benign tumor, treatment is challenging because of the tumor's eloquent location. Today, with the exception of surgical intervention and irradiation, further treatment options are limited. However, ongoing molecular research in this field provides insights into the pathways involved in ACP pathogenesis and reveal a plethora of druggable targets. Read More

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