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Journal of Neuropathology and Experimental Neurology

Tiziano Balzano, Jerónimo Forteza, Irene Borreda, Pilar Molina, Juan Giner, Paola Leone, Amparo Urios, Carmina Montoliu, Vicente Felipo
Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) affect 29 million people in the European Union. Patients with ASH and NASH may exhibit cognitive impairment, reducing their quality of life. Steatohepatitis induces cerebral alterations. It is not known if histological analysis could allow distinguishing ASH, NASH, and/or cirrhosis neuropathology and other entities. The aim of this work was to analyze a set of histopathological features characterizing the brain lesions due to ASH, NASH, and cirrhosis...
July 16, 2018: Journal of Neuropathology and Experimental Neurology
Hsin-Yi Wu, Po-Cheng Kuo, Yi-Ting Wang, Hao-Tai Lin, Allyson D Roe, Bo Y Wang, Chia-Li Han, Bradley T Hyman, Yu-Ju Chen, Hwan-Ching Tai
A synergy between β-amyloid (Aβ) and tau appears to occur in Alzheimer disease (AD), but the mechanisms of interaction, and potential locations, are little understood. This study investigates the possibility of such interactions within the cortical synaptic compartments of APP/PS1 mice. We used label-free quantitative mass spectrometry to study the phosphoproteome of synaptosomes, covering 2400 phosphopeptides and providing an unbiased survey of phosphorylation changes associated with amyloid pathology. Hyperphosphorylation was detected on 36 synaptic proteins, many of which are associated with the cytoskeleton...
July 16, 2018: Journal of Neuropathology and Experimental Neurology
Lilah M Besser, Walter A Kukull, Merilee A Teylan, Eileen H Bigio, Nigel J Cairns, Julia K Kofler, Thomas J Montine, Julie A Schneider, Peter T Nelson
Neuropathologic evaluation remains the gold standard for determining the presence and severity of aging-related neurodegenerative diseases. Researchers at U.S. Alzheimer's Disease Centers (ADCs) have worked for >30 years studying human brains, with the goals of achieving new research breakthroughs. Harmonization and sharing among the 39 current and past ADCs is promoted by the National Alzheimer's Coordinating Center (NACC), which collects, audits, and disburses ADC-derived data to investigators on request...
June 25, 2018: Journal of Neuropathology and Experimental Neurology
Mathilde Duchesne, Olivier Roussellet, Thierry Maisonobe, Nathalie Gachard, David Rizzo, Marine Armand, Karine Viala, Laurence Richard, Manuela Delage-Corre, Arnaud Jaccard, Philippe Corcia, Jean-Michel Vallat, Laurent Magy
Infiltration of the peripheral nervous system (PNS) by lymphoma, called neurolymphomatosis, is a rare condition among the spectrum of lymphoma-associated neuropathies; its diagnosis is challenging. Cerebrospinal fluid (CSF) analysis is of great value, but nerve biopsy (NB) may be necessary to prove invasion by malignant cells. Clonality polymerase chain reaction (PCR)-based analysis is a validated method in the diagnosis of hematological malignancies, but there are very little data on its diagnostic yield on NB samples...
June 23, 2018: Journal of Neuropathology and Experimental Neurology
Yasuaki Ogino, Michal Vascak, John T Povlishock
Mild traumatic brain injury (mTBI) has been linked to enduring neurological damage following repetitive injury. Previously, we reported that intensity-specific, repetitive mTBI exacerbated microvascular and axonal damage in brainstem. For a more rigorous and global assessment, we assessed the burden of neocortical diffuse axonal injury (DAI) evoked by repetitive mTBI. Mice were subjected to mild central fluid percussion injuries at 1.4 and 1.6 atm with or without repetitive insult at a 3-hour interval and killed at 24 hours postinjury...
June 22, 2018: Journal of Neuropathology and Experimental Neurology
Jennifer H Kang, Anne F Buckley, Seema Nagpal, Nancy Fischbein, Katherine B Peters
Prior to their provisional WHO classification as a distinct entity in 2016, diffuse leptomeningeal glioneuronal tumors (DLGNT) were often regarded as diffuse leptomeningeal presentations of oligodendrogliomas or extraventricular neurocytomas. Their classification as a distinct entity partly relies on their pattern of growth, but DLGNTs without radiological leptomeningeal involvement have been described. In a patient with a DLGNT of the spinal cord without evidence of leptomeningeal involvement, we review in depth the clinical course and the histologic and molecular features of the neoplasm, in the context of other reported cases without diffuse leptomeningeal involvement...
June 20, 2018: Journal of Neuropathology and Experimental Neurology
Julia Velz, Abbas Agaimy, Karl Frontzek, Marian Christoph Neidert, Oliver Bozinov, Ulrich Wagner, Christine Fritz, Roland Coras, Silvia Hofer, Beata Bode-Lesniewska, Elisabeth Rushing
Primary intracranial neoplasms with features of extraskeletal myxoid chondrosarcomas (EMC) are extremely rare and poorly characterized tumors with only ∼12 cases described, the majority lacking molecular confirmation. There is an urgent need for the integration of molecular studies for correct subclassification of these tumors in order to predict clinical behavior, guide therapeutic decision-making, and provide novel targets for therapy. Clinical and pathologic data of 3 intracranial EMC-like myxoid neoplasms were retrospectively reviewed...
June 18, 2018: Journal of Neuropathology and Experimental Neurology
Zhe Li, Xuezhao Cao, Hong Ma, Yong Cui, Xiaoqian Li, Na Wang, Yongjian Zhou
Age is the most prominent risk factor for the development of postoperative cognitive dysfunction. The present study investigated the role of CX3CL1-CX3CR1 signaling in age-related differences in surgery-induced cognitive deficits and neuroinflammation. Adult and aged male Sprague-Dawley rats were subjected to partial hepatectomy or partial hepatectomy with intracerebroventricular infusion of CX3CL1. On postoperative days 3, 7, and 14, the rats were subjected to an open field test and the Morris water maze test...
May 31, 2018: Journal of Neuropathology and Experimental Neurology
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May 31, 2018: Journal of Neuropathology and Experimental Neurology
David S Priemer, Darrell D Davidson, Patrick J Loehrer, Sunil S Badve
Thymomas are associated with autoantibody formation. The most common are anti-acetylcholine receptor antibodies, which correspond to myasthenia gravis (MG). Other autoantibodies, such as antistriational antibodies, can occur, but their relation to clinical syndromes is frequently uncertain. The etiology of antistriational antibodies is also poorly understood. In this case, a 61-year-old man with a history of thymoma was admitted with respiratory failure. The patient was positive for anti-acetylcholine receptor antibodies and antistriational antibodies...
May 29, 2018: Journal of Neuropathology and Experimental Neurology
Emily M Siebers, Melinda J Choi, Jennifer A Tinklenberg, Margaret J Beatka, Samuel Ayres, Hui Meng, Daniel C Helbling, Akiko Takizawa, Brian Bennett, Alexander M Garces, Luiz-Gabriel Dias Duarte Machado, David Dimmock, Melinda R Dwinell, Aron M Geurts, Michael W Lawlor
Mitochondrial diseases (MDs) result from alteration of the mitochondrial respiratory chain (MRC) function. Despite the prevalence of MDs in the population, the paucity of animal models available limits the understanding of these disorders. Mutations in SDHA, a gene that codes for the alpha subunit of succinate dehydrogenase (SDH), can cause some forms of MD. SDHA is a crucial contributor to MRC function. In order to expand the range of MD animal models available, we attempted to generate a Sdha knockout rat...
May 8, 2018: Journal of Neuropathology and Experimental Neurology
Diana Cantero, Ángel Rodríguez de Lope, Raquel Moreno de la Presa, Juan M Sepúlveda, José M Borrás, Javier S Castresana, Nicky D'Haene, Juan F García, Isabelle Salmon, Manuela Mollejo, Juan A Rey, Aurelio Hernández-Laín, Bárbara Meléndez
Glioblastoma (GBM) is the most common malignant adult primary brain tumor. Despite its high lethality, a small proportion of patients have a relatively long overall survival (OS). Here we report a study of a series of 74 GBM samples from 29 long-term survivors ([LTS] OS ≥36 months) and 45 non-LTS. Using next-generation sequencing, we analyzed genetic alterations in the genes most frequently altered in gliomas. Approximately 20% of LTS had a mutation in the IDH1 or IDH2 (IDH) genes, denoting the relevance of this molecular prognostic factor...
August 1, 2018: Journal of Neuropathology and Experimental Neurology
Oscar Ramos-Campoy, Rainiero Ávila-Polo, Oriol Grau-Rivera, Anna Antonell, Jordi Clarimón, Ricardo Rojas-García, Sara Charif, Veronica Santiago-Valera, Isabel Hernandez, Miquel Aguilar, Consuelo Almenar, Dolores Lopez-Villegas, Lorena Bajo, Pau Pastor, Julie Van der Zee, Albert Lladó, Raquel Sanchez-Valle, Ellen Gelpi
The neuropathological hallmark of the C9orf72 intronic hexanucleotide expansion in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) is the presence of small ubiquitin/p62-positive and transactive response DNA binding protein 43 kDa (TDP-43)-negative cytoplasmic inclusions in several brain areas. The identification of this histopathological signature is highly predictive of an underlying mutation. In this study, we screened 1800 cases of the Barcelona IDIBAPS Brain Bank, independently of the clinical and final neuropathological diagnosis of the brain donor, for the presence of ubiquitin/p62-positive inclusions in the cerebellum (UPPI)...
August 1, 2018: Journal of Neuropathology and Experimental Neurology
Aušrine Areškeviciute, Linea Cecilie Melchior, Helle Broholm, Lars-Henrik Krarup, Suzanne Granhøj Lindquist, Peter Johansen, Neil McKenzie, Alison Green, Jørgen Erik Nielsen, Henning Laursen, Eva Løbner Lund
This is the first report of presumed sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Sträussler-Scheinker disease (GSS) with the prion protein gene c.305C>T mutation (p.P102L) occurring in one family. The father and son were affected with GSS and the mother had a rapidly progressive form of CJD. Diagnosis of genetic, variant, and iatrogenic CJD was ruled out based on the mother's clinical history, genetic tests, and biochemical investigations, all of which supported the diagnosis of sCJD. However, given the low incidence of sCJD and GSS, their co-occurrence in one family is extraordinary and challenging...
August 1, 2018: Journal of Neuropathology and Experimental Neurology
Eric M Thompson, Michael Brown, Elena Dobrikova, Vijay Ramaswamy, Michael D Taylor, Roger McLendon, Jennifer Sanks, Vidya Chandramohan, Darell Bigner, Matthias Gromeier
Poliovirus oncolytic immunotherapy is a putatively novel approach to treat pediatric brain tumors. This work sought to determine expression of the poliovirus receptor (PVR), CD155, in low-grade and malignant pediatric brain tumors and its ability to infect, propagate, and inhibit cell proliferation. CD155 expression in pleomorphic xanthoastrocytoma (PXA), medulloblastoma, atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, and anaplastic ependymoma specimens was assessed. The ability of the polio: rhinovirus recombinant, PVSRIPO, to infect PXA (645 [BRAF V600E mutation], 2363) and medulloblastoma (D283, D341) cells were determined by viral propagation measurement and cell proliferation...
August 1, 2018: Journal of Neuropathology and Experimental Neurology
Alexander J Moszczynski, Jason Gopaul, Patrick McCunn, Kathryn Volkening, Madeline Harvey, Robert Bartha, Susanne Schmid, Michael J Strong
Aberrant phosphorylation of the microtubule associated protein tau (tau) is associated with multiple neurodegenerative diseases where it is a contributes to neurotoxicity. We have observed that phosphorylation at Thr175 tau (pThr175 tau) exerts toxicity when expressed as a pseudophosphorylated tau construct (Thr175Asp) in vitro. To determine whether pThr175 tau can induce tau pathology in vivo with an accompanying clinical phenotype, we used a recombinant adenoviral expression vector (rAAV9) to express a GFP-tagged Thr175Asp tau protein construct in adult female Sprague-Dawley rat hippocampus...
August 1, 2018: Journal of Neuropathology and Experimental Neurology
Leomar Y Ballester, Isabella C Glitza Oliva, Dzifa Y Douse, Melissa M Chen, Chieh Lan, Lauren E Haydu, Jason T Huse, Sinchita Roy-Chowdhuri, Rajyalakshmi Luthra, Ignacio I Wistuba, Michael A Davies
Circulating tumor DNA (ctDNA) refers to tumor-derived cell-free DNA that circulates in body fluids. Fluid samples are easier to collect than tumor tissue, and are amenable to serial collection at multiple time points during the course of a patient's illness. Studies have demonstrated the feasibility of performing mutation profiling from blood samples in cancer patients. However, detection of ctDNA in the blood of patients with brain tumors is suboptimal. Cerebrospinal fluid (CSF) can be obtained via lumbar puncture or intraventricular catheter, and may be a suitable fluid to assess ctDNA in patients with brain tumors...
July 1, 2018: Journal of Neuropathology and Experimental Neurology
Aoife P Kiely, Christina E Murray, Sandrine C Foti, Bridget C Benson, Robert Courtney, Catherine Strand, Tammaryn Lashley, Janice L Holton
Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease characterized by aggregation of α-synuclein in oligodendrocytes to form glial cytoplasmic inclusions. According to the distribution of neurodegeneration, MSA is subtyped as striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA), or as combination of these 2 (mixed MSA). In the current study, we aimed to investigate regional microglial populations and gene expression in the 3 different MSA subtypes. Microscopy with microglial marker Iba-1 combined with either proinflammatory marker CD68 or anti-inflammatory marker Arginase-1 was analyzed in control, SND, and OPCA cases (n = 5) using paraffin embedded sections...
July 1, 2018: Journal of Neuropathology and Experimental Neurology
Lee J Martin, Qing Chang
Neurological disorders affecting individuals in infancy to old age elude interventions for meaningful protection against neurodegeneration, and preclinical work has not translated to humans. We studied human neuron responses to injury and death stimuli compared to those of animal neurons in culture under similar settings of insult (excitotoxicity, oxidative stress, and DNA damage). Human neurons were differentiated from a cortical neuron cell line and the embryonic stem cell-derived H9 line. Mouse neurons were differentiated from forebrain neural stem cells and embryonic cerebral cortex; pig neurons were derived from forebrain neural stem cells...
July 1, 2018: Journal of Neuropathology and Experimental Neurology
Pol Andrés-Benito, Ellen Gelpi, Mónica Povedano, Gabriel Santpere, Isidro Ferrer
Molecular alterations compromising key metabolic pathways are poorly understood in sporadic frontotemporal lobar degeneration with TDP-43 pathology (sFTLD-TDP). Whole-transcriptome array, RT-qPCR validation, gel electrophoresis, and Western blotting, and mitochondrial electron transport chain (ETC) activity were comparatively examined in frontal cortex (area 8) of 16 sFTLD-TDP cases and 14 controls. Assessment of 111 genes by RT-qPCR showed deregulation of 81 genes linked to neurotransmission and synapses, neuronal architecture, cytoskeleton of axons and dendrites, vesicle trafficking, purines, mitochondria, and energy metabolism in sFTLD-TDP...
July 1, 2018: Journal of Neuropathology and Experimental Neurology
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