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Journal of Neuropathology and Experimental Neurology

Gabor G Kovacs, Sharon X Xie, Edward B Lee, John L Robinson, Carrie Caswell, David J Irwin, Jon B Toledo, Victoria E Johnson, Douglas H Smith, Irina Alafuzoff, Johannes Attems, Janos Bencze, Kevin F Bieniek, Eileen H Bigio, Istvan Bodi, Herbert Budka, Dennis W Dickson, Brittany N Dugger, Charles Duyckaerts, Isidro Ferrer, Shelley L Forrest, Ellen Gelpi, Stephen M Gentleman, Giorgio Giaccone, Lea T Grinberg, Glenda M Halliday, Kimmo J Hatanpaa, Patrick R Hof, Monika Hofer, Tibor Hortobágyi, James W Ironside, Andrew King, Julia Kofler, Enikö Kövari, Jillian J Kril, Seth Love, Ian R Mackenzie, Qinwen Mao, Radoslav Matej, Catriona McLean, David G Munoz, Melissa E Murray, Janna Neltner, Peter T Nelson, Diane Ritchie, Roberta D Rodriguez, Zdenek Rohan, Annemieke Rozemuller, Kenji Sakai, Christian Schultz, Danielle Seilhean, Vanessa Smith, Pawel Tacik, Hitoshi Takahashi, Masaki Takao, Dietmar Rudolf Thal, Serge Weis, Stephen B Wharton, Charles L White, John M Woulfe, Masahito Yamada, John Q Trojanowski
Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview...
June 7, 2017: Journal of Neuropathology and Experimental Neurology
Seyed Esmaeil Khoshnam, William Winlow, Maryam Farzaneh
Immunity and inflammation are important parameters of the pathophysiology of stroke, a destructive illness that is the second most common cause of death worldwide. Following ischemic stroke, neuroinflammation plays a critical role in neurodegeneration and brain injury. MicroRNAs (miRNAs) are a class of endogenously expressed, noncoding RNA molecules that function to inhibit mRNA translation. Recent studies demonstrate that miRNAs are key regulators of inflammatory processes contributing to ischemic stroke injuries...
May 23, 2017: Journal of Neuropathology and Experimental Neurology
Catherine D Kim, Ryan E Reed, Meredith A Juncker, Zhide Fang, Shyamal D Desai
Interferon-stimulated gene 15 (ISG15), an antagonist of the ubiquitin pathway, is elevated in cells and brain tissues obtained from ataxia telangiectasia (A-T) patients. Previous studies reveal that an elevated ISG15 pathway inhibits ubiquitin-dependent protein degradation, leading to activation of basal autophagy as a compensatory mechanism for protein turnover in A-T cells. Also, genotoxic stress (ultraviolet [UV] radiation) deregulates autophagy and induces aberrant degradation of ubiquitylated proteins in A-T cells...
May 23, 2017: Journal of Neuropathology and Experimental Neurology
Guoming Luan, Xiongfei Wang, Qing Gao, Yuguang Guan, Jing Wang, Jiahui Deng, Feng Zhai, Yin Chen, Tianfu Li
Rasmussen encephalitis (RE) is a rare neurological disorder characterized by unilateral inflammation of cerebral cortex and other structures, most notably the hippocampus, progressive cognitive deterioration, and pharmacoresistant focal epilepsy. The pathogenesis of RE with unilateral cortical atrophy and focal seizures is still enigmatic. Activation of adenosine A1 receptors (A1R) has been proven to prevent the spatial spread of seizures. We hypothesized that the epileptogenic mechanisms underlying RE are related to changes in neuronal A1R expression...
August 1, 2017: Journal of Neuropathology and Experimental Neurology
Fengyan Zhao, Yi Qu, Jianghu Zhu, Li Zhang, Lan Huang, Haiting Liu, Shiping Li, Dezhi Mu
Increasing evidence has demonstrated a vital role of microRNAs (miRNAs) in diverse biological processes. However, their functions in developing brain with hypoxia-ischemia (HI) remain largely unknown. Through a miRNA microarray analysis in a P10 rat model of cerebral HI, we found that miR-30d-5p was one of the most deregulated miRNAs in neonatal brains in response to HI. MiR-30d-5p was downregulated in a time-dependent manner in brain cortex after HI, which was accompanied by increased expression of Beclin1 both at transcript and protein levels...
August 1, 2017: Journal of Neuropathology and Experimental Neurology
Alyssa B Becker, Jiang Qian, Benjamin B Gelman, Michele Yang, Peter Bauer, Arnulf H Koeppen
In a small percentage of patients with Friedreich ataxia (FA), the pathogenic mutation is compound heterozygous, consisting of a guanine-adenine-adenine (GAA) trinucleotide repeat expansion in one allele, and a deletion, point mutation, or insertion in the other. In 2 cases of compound heterozygous FA, the GAA expansion was inherited from the mother, and deletions from the father. Compound heterozygous FA patient 1, an 11-year-old boy (GAA, 896/c.11_12TCdel), had ataxia, chorea, cardiomyopathy, and diabetes mellitus...
August 1, 2017: Journal of Neuropathology and Experimental Neurology
Takayasu Mishima, Shunsuke Koga, Wen-Lang Lin, Koji Kasanuki, Monica Castanedes-Casey, Zbigniew K Wszolek, Shin J Oh, Yoshio Tsuboi, Dennis W Dickson
Perry syndrome is a rare atypical parkinsonism with depression, apathy, weight loss, and central hypoventilation caused by mutations in dynactin p150glued (DCTN1). A rare distal hereditary motor neuropathy, HMN7B, also has mutations in DCTN1. Perry syndrome has TAR DNA-binding protein of 43 kDa (TDP-43) inclusions as a defining feature. Other TDP-43 proteinopathies include amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with and without motor neuron disease (FTLD-MND). TDP-43 forms aggregates in neuronal cytoplasmic inclusions (NCIs), neuronal intranuclear inclusions, dystrophic neurites (DNs), as well as axonal spheroids, oligodendroglial cytoplasmic inclusions, and perivascular astrocytic inclusions (PVIs)...
August 1, 2017: Journal of Neuropathology and Experimental Neurology
Malgorzata Ziemka-Nalecz, Joanna Jaworska, Teresa Zalewska
Neonatal hypoxia-ischemia (HI) is one of the major causes of death and/or lifelong neurobehavioral and cognitive dysfunction. Undoubtedly, brain damage following HI insult is a complex process with multiple contributing mechanisms and pathways resulting in both early and delayed injury. It is increasingly recognized that one of the leading pathogenic factors of neonatal brain damage is inflammation, induced by activation of the central and peripheral immune system. Immune responses are induced within minutes and can expand for weeks and even months after the insult...
August 1, 2017: Journal of Neuropathology and Experimental Neurology
Yvonne Schweizer, Zsolt Meszaros, David T W Jones, Christian Koelsche, Miream Boudalil, Petra Fiesel, Daniel Schrimpf, Rosario M Piro, Stefanie Brehmer, Andreas von Deimling, Ulrich Kerl, Marcel Seiz-Rosenhagen, David Capper
Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a highly malignant, pediatric brain tumor typically arising de novo. Inactivation of SMARCB1 is a defining molecular event. We present here a rare case of an adult (35 years) low-grade SMARCB1-deleted brain tumor with transition into prototypical AT/RT over 14 years. Molecular analysis was performed for 3 tumor presentations including copy number analysis, DNA methylation analysis (450k), and whole exome sequencing. We detected the identical somatic SMARCB1 deletion at all 3 time-points...
August 1, 2017: Journal of Neuropathology and Experimental Neurology
Drew Pratt, Stefania Pittaluga, Maryknoll Palisoc, Patricia Fetsch, Liqiang Xi, Mark Raffeld, Mark R Gilbert, Martha Quezado
Glioblastoma is an aggressive, often recalcitrant disease. In the majority of cases, prognosis is dismal and current therapies only moderately prolong survival. Immunotherapy is increasingly being recognized as an effective treatment modality. CD70 is a transmembrane protein that shows restricted expression in tissue but has been described in various malignancies. Therapeutic targeting of CD70 has demonstrated antitumor efficacy and is in clinical trials. Here, we sought to characterize CD70 expression in a large cohort of gliomas (n = 205) using tissue microarrays...
August 1, 2017: Journal of Neuropathology and Experimental Neurology
Daniel J Shepherd, Shih-Yen Tsai, Stefanie P Cappucci, Joanna Y Wu, Robert G Farrer, Gwendolyn L Kartje
Ischemic stroke is a leading cause of adult disability with no pharmacological treatments to promote the recovery of lost function. Neutralizing antibodies against the neurite outgrowth inhibitor Nogo-A have emerged as a promising treatment for subacute and chronic stroke in animal models; however, whether anti-Nogo-A treatment affects poststroke neurogenesis remains poorly understood. In this study, we confirmed expression of Nogo-A by neuroblasts in the adult rat subventricular zone (SVZ), a major neurogenic niche; however, we found no evidence that Nogo-A was expressed at the surface of these cells...
August 1, 2017: Journal of Neuropathology and Experimental Neurology
Jerzy Wegiel, Michael Flory, Izabela Kuchna, Krzysztof Nowicki, Shuang Yong Ma, Jarek Wegiel, Eulalia Badmaev, Wayne P Silverman, Mony de Leon, Barry Reisberg, Thomas Wisniewski
Increase in human life expectancy has resulted in the rapid growth of the elderly population with minimal or no intellectual deterioration. The aim of this stereological study of 10 structures and 5 subdivisions with and without neurofibrillary degeneration in the brains of 28 individuals 25-102-years-old was to establish the pattern of age-associated neurodegeneration and neuronal loss in the brains of nondemented adults and elderly. The study revealed the absence of significant neuronal loss in 7 regions and topographically selective reduction of neuronal reserve over 77 years in 8 brain structures including the entorhinal cortex (EC) (-33...
June 1, 2017: Journal of Neuropathology and Experimental Neurology
Jordon Dunham, Jan Bauer, Graham R Campbell, Don J Mahad, Nikki van Driel, Susanne M A van der Pol, Bert A 't Hart, Hans Lassmann, Jon D Laman, Jack van Horssen, Yolanda S Kap
Oxidative damage and iron redistribution are associated with the pathogenesis and progression of multiple sclerosis (MS), but these aspects are not entirely replicated in rodent experimental autoimmune encephalomyelitis (EAE) models. Here, we report that oxidative burst and injury as well as redistribution of iron are hallmarks of the MS-like pathology in the EAE model in the common marmoset. Active lesions in the marmoset EAE brain display increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p22phox, p47phox, and gp91phox) and inducible nitric oxide synthase immunoreactivity within lesions with active inflammation and demyelination, coinciding with enhanced expression of mitochondrial heat-shock protein 70 and superoxide dismutase 1 and 2...
June 1, 2017: Journal of Neuropathology and Experimental Neurology
Caitlin S Latimer, C Dirk Keene, Margaret E Flanagan, Laura S Hemmy, Kelvin O Lim, Lon R White, Kathleen S Montine, Thomas J Montine
Two population-based studies key to advancing knowledge of brain aging are the Honolulu-Asia Aging Study (HAAS) and the Nun Study. Harmonization of their neuropathologic data allows cross comparison, with findings common to both studies likely generalizable, while distinct observations may point to aging brain changes that are dependent on sex, ethnicity, environment, or lifestyle factors. Here, we expanded the neuropathologic evaluation of these 2 studies using revised NIA-Alzheimer's Association guidelines and compared directly the neuropathologic features of resistance and apparent cognitive resilience...
June 1, 2017: Journal of Neuropathology and Experimental Neurology
Nathan A Dahl, Timothy Luebbert, Michele Loi, Ilana Neuberger, Michael H Handler, Bette Kay Kleinschmidt-DeMasters, Jean M Mulcahy Levy
Chordomas are rare bony neoplasms usually unassociated with a familial tumor predisposition syndrome. The peak incidence of this midline axial skeletal tumor is in adulthood but when very young children are affected, consideration should be given to occurrence within the tuberous sclerosis (TS) complex, especially when presenting in neonates <3 months of age. To call attention to this association, we present a brachyury-immunopositive chordoma occurring in the skull base of a 2-month-old male infant who was later realized to have metastases to the subcutaneous tissues and lungs, as well as rhabdomyoma of the heart and renal cysts/angiomyolipomas, that is, characteristic features of the TS complex...
June 1, 2017: Journal of Neuropathology and Experimental Neurology
Isabel S Goldstein, Drexel J Erickson, Lynn A Sleeper, Robin L Haynes, Hannah C Kinney
Abnormalities of lateral temporal lobe development are associated with a spectrum of genetic and environmental pathologic processes, but more normative data are needed for a better understanding of gyrification in this brain region. Here, we begin to establish guidelines for the analysis of the lateral temporal lobe in humans in early life. We present quantitative methods for measuring gyrification at autopsy using photographs of the gross brain and simple computer-based quantitative tools in a cohort of 28 brains ranging in age from 27 to 70 postconceptional weeks (end of infancy)...
June 1, 2017: Journal of Neuropathology and Experimental Neurology
Matthew Torre, Mirna Lechpammer, Vera Paulson, Sanjay Prabhu, Audrey C Marshall, Amy L Juraszek, Robert F Padera, Elizabeth A Bundock, Sara O Vargas, Rebecca D Folkerth
Upon detection of foreign-body embolization to the central nervous system (CNS) following a specific invasive cardiovascular procedure in 1 autopsied child, we undertook a quality assurance analysis to determine whether other patients had had similar events. Autopsies of all infants and children with history of cardiac catheterization, heart surgery on cardiopulmonary bypass, and/or extracorporeal membrane oxygenation over a 5-year period at a single tertiary care institution were reviewed for light-microscopic evidence of foreign material...
May 19, 2017: Journal of Neuropathology and Experimental Neurology
Eva M M Strijbis, Evert-Jan Kooi, Paul van der Valk, Jeroen J G Geurts
Cortical lesions (CLs) are an important component of multiple sclerosis (MS) pathology; they correlate better with physical disability and cognitive impairment than white matter lesions (WMLs). Because remyelination can be extensive in CLs, we quantified remyelination in gray matter (GM) and white matter (WM), addressing oligodendrocyte (OGD) maturation state and clinical relevance of remyelination. Brain tissue samples from 21 chronic MS patients were immunohistochemically stained for myelin proteolipid protein, Olig2, which is strongly expressed in OGD precursor cells (OPCs), but weakly expressed in mature OGDs and other OGD markers...
May 1, 2017: Journal of Neuropathology and Experimental Neurology
Valeria Barresi, Maria Caffo
No abstract text is available yet for this article.
May 1, 2017: Journal of Neuropathology and Experimental Neurology
James P McAllister, Maria Montserrat Guerra, Leandro Castaneyra Ruiz, Antonio J Jimenez, Dolores Dominguez-Pinos, Deborah Sival, Wilfred den Dunnen, Diego M Morales, Robert E Schmidt, Esteban M Rodriguez, David D Limbrick
To determine if ventricular zone (VZ) and subventricular zone (SVZ) alterations are associated with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus, we compared postmortem frontal and subcortical brain samples from 12 infants with IVH and 3 nonneurological disease controls without hemorrhages or ventriculomegaly. Birth and expiration estimated gestational ages were 23.0-39.1 and 23.7-44.1 weeks, respectively; survival ranges were 0-42 days (median, 2.0 days). Routine histology and immunohistochemistry for neural stem cells (NSCs), neural progenitors (NPs), multiciliated ependymal cells (ECs), astrocytes (AS), and cell adhesion molecules were performed...
May 1, 2017: Journal of Neuropathology and Experimental Neurology
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