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Journal of Neuropathology and Experimental Neurology

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https://www.readbyqxmd.com/read/27818385/contactin-associated-protein-1-cntnap1-mutations-induce-characteristic-lesions-of-the-paranodal-region
#1
Jean-Michel Vallat, Mathilde Nizon, Alex Magee, Bertrand Isidor, Laurent Magy, Yann Péréon, Laurence Richard, Robert Ouvrier, Benjamin Cogné, Jérôme Devaux, Stephan Zuchner, Stéphane Mathis
Congenital hypomyelinating neuropathy is a rare neonatal syndrome responsible for hypotonia and weakness. Nerve microscopic examination shows amyelination or hypomyelination. Recently, mutations in CNTNAP1 have been described in a few patients. CNTNAP1 encodes contactin-associated protein 1 (caspr-1), which is an essential component of the paranodal junctions of the peripheral and central nervous systems, and is necessary for the establishment of transverse bands that stabilize paranodal axo-glial junctions...
November 6, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27815397/new-strategy-that-delays-progression-of-amyotrophic-lateral-sclerosis-in-g1h-g93a-transgenic-mice-oral-administration-of-xanthine-oxidoreductase-inhibitors-that-are-not-substrates-for-the-purine-salvage-pathway
#2
Shinsuke Kato, Masako Kato, Teruo Kusano, Takeshi Nishino
Amyotrophic lateral sclerosis (ALS), Lou Gehrig's disease, is a progressive fatal neurodegenerative disease that involves both upper and lower motor neurons. We orally administered 4 xanthine oxidoreductase (XOR) inhibitors to G1H-G93A mice carrying 25 transgene copy numbers of human mutant G93A superoxide dismutase 1, from 80 days of age. Three nonpurine-analogue inhibitors (TEI-6720: Febuxostat, Y-700 and FYX-051), but not allopurinol with a purine analogue ring (pyrazolo pyrimidine ring), significantly delayed disease onset, prolonged survival and the duration of disease stages, improved clinical signs, and alleviated weight loss...
November 4, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27815396/quantitative-analysis-of-the-cellular-microenvironment-of-glioblastoma-to-develop-predictive-statistical-models-of-overall-survival
#3
Jessica X Yuan, Fahad F Bafakih, James W Mandell, Bethany J Horton, Jennifer M Munson
Glioblastomas, the most common primary malignant brain tumors, have a distinct tissue microenvironment. Although non-neoplastic cells contribute to glioblastoma progression, very few quantitative studies have shown the effect of tumor microenvironmental influences on patient survival. We examined relationships of the cellular microenvironment, including astrocytes, microglia, oligodendrocytes, and blood vessels, to survival in glioblastoma patients. Using histological staining and quantitative image analyses, we examined the tumor-associated parenchyma of 33 patients and developed statistical models to predict patient outcomes based on the cellular picture of the tumor parenchyma...
November 4, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27815395/chronic-traumatic-encephalopathy-like-abnormalities-in-a-routine-neuropathology-service
#4
Shawna Noy, Sherry Krawitz, Marc R Del Bigio
Chronic traumatic encephalopathy (CTE) has been described mainly in professional athletes and military personnel and is characterized by deposition of hyperphosphorylated tau at the depths of cortical sulci and around blood vessels. To assess CTE-like changes in a routine neuropathology service, we prospectively examined 111 brains (age 18-60 years). The presence of tau-immunoreactive deposits was staged using guidelines described by others and was correlated with the medical history. 72/111 cases were negative for CTE-like changes; 34/111 were CTE stage <1; 3/111 were CTE stage 1; and 2/111 were CTE stage 2...
November 4, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27807004/endothelial-cell-hypertrophy-and-microvascular-proliferation-in-meningiomas-are-correlated-with-higher-histological-grade-and-shorter-progression-free-survival
#5
Catherine Ling, Celso Pouget, Fabien Rech, Robin Pflaum, Mathilde Treffel, Franck Bielle, Karima Mokhtari, Jean-Matthieu Casse, Jean-Michel Vignaud, Michel Kalamarides, Matthieu Peyre, Guillaume Gauchotte
Microvascular proliferation (MVP) is a hallmark of glioblastoma. Endothelial cell hypertrophy (ECH), also known as endothelial hyperplasia, is correlated with a shorter survival of patients with gliomas. However, the prognostic value of these 2 morphological features has not been studied in meningiomas. The aim of this study was to evaluate the prognostic value of angiogenesis in meningiomas, most notably ECH, MVP, and microvascular density, which were evaluated using immunohistochemistry with antibodies against CD34 and CD105 (a marker of neovascularization) in a series of 139 meningiomas...
November 2, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27694117/radiation-induced-cerebral-vascular-malformations-at-biopsy
#6
B K Kleinschmidt-DeMasters, Kevin O Lillehei
Radiation-induced vascular "malformations", designated cavernous hemangiomas/cavernomas ("RICHs"), are seldom biopsied and are usually diagnosed based on neuroimaging features. They are an increasingly recognized complication of both CNS external beam radiation therapy and stereotactic radiosurgery. We identified 13 patients with radiation-induced vascular "malformations" in our surgical neuropathology databases searched from 2000 to 2016; 4 had received their therapy during childhood; 5 had received radiosurgery...
September 30, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27678346/shared-and-distinct-patterns-of-oligodendroglial-response-in-%C3%AE-synucleinopathies-and-tauopathies
#7
Zdenek Rohan, Ivan Milenkovic, Mirjam I Lutz, Radoslav Matej, Gabor G Kovacs
Pathological protein deposits in oligodendroglia are common but variable features of various neurodegenerative conditions. To evaluate oligodendrocyte response in neurodegenerative diseases (NDDs) with different extents of oligodendroglial protein deposition we performed immunostaining for tubulin polymerization-promoting protein p25α (TPPP/p25α), α-synuclein (α-syn), phospho-tau, ubiquitin, myelin basic protein, and the microglial marker HLA-DR. We investigated cases of multiple system atrophy ([MSA] n = 10), Lewy body disease ([LBD] n = 10), globular glial tauopathy ([GGT] n = 7) and progressive supranuclear palsy ([PSP] n = 10)...
September 26, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27667772/t-cells-underlie-some-but-not-all-of-the-cerebellar-pathology-in-a-neonatal-rat-model-of-congenital-lymphocytic-choriomeningitis-virus-infection
#8
Hannah Klein, Glenda K Rabe, Bahri Karacay, Daniel J Bonthius
Lymphocytic choriomeningitis virus (LCMV) infection during pregnancy injures the human fetal brain. Neonatal rats inoculated with LCMV are an excellent model of congenital LCMV infection because they develop cerebellar injuries similar to those in humans. To evaluate the role of T-lymphocytes in LCMV-induced cerebellar pathology, congenitally athymic rats, deficient in T-lymphocytes were compared with euthymic rats. Peak viral titers and cellular targets of infection were similar, but viral clearance from astrocytes was impaired in the athymic rats...
September 25, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27634965/c-terminal-deleted-prion-protein-fragment-is-a-major-accumulated-component-of-systemic-prp-deposits-in-hereditary-prion-disease-with-a-2-bp-ct-deletion-in-prnp-codon-178
#9
Hiroyuki Honda, Kosuke Matsuzono, Soichiro Fushimi, Kota Sato, Satoshi O Suzuki, Koji Abe, Toru Iwaki
Prion protein (PrP) has 2 glycosylated sites and a glycosylphosphatidylinositol (GPI) anchor on the C-terminal. Reports on genetic prion disease with GPI anchorless PrP are very limited. In this study, we characterized the molecular alterations of mutated PrP in a 37-year-old female autopsy case with a recently identified PRNP mutation involving a 2-bp deletion in codon 178 that results in a premature stop codon mutation in codon 203. Postmortem examination revealed numerous irregularly shaped coarse PrP deposits and multicentric plaques in the brain that were mainly comprised of C-terminal deleted abnormal PrP primarily derived from the mutant allele...
September 15, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27634964/effect-of-inhibition-or-deletion-of-neutral-endopeptidase-on-neuropathic-endpoints-in-high-fat-fed-low-dose-streptozotocin-treated-mice
#10
Matthew S Yorek, Alexander Obrosov, Bao Lu, Craig Gerard, Randy H Kardon, Mark A Yorek
Previously we demonstrated that a vasopeptidase inhibitor of angiotensin converting enzyme and neutral endopeptidase (NEP), a protease that degrades vaso- and neuro-active peptides, improves neural function in diabetic rodent models. The purpose of this study was to determine whether inhibition or deletion of NEP provides protection from neuropathy caused by diabetes with an emphasis on morphology of corneal nerves as a primary endpoint. Diabetes, modeling type 2, was induced in C57Bl/6J and NEP deficient mice through a combination of a high fat diet and streptozotocin...
September 15, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27634963/pediatric-neuropathology-in-africa-local-experience-in-nigeria-and-challenges-and-prospects-for-the-continent
#11
Babatunde J Olasode, Chiazor U Onyia
The present state of pediatric neuropathology practice is in rudimentary developmental stages in most parts of sub-Saharan Africa. We sought to determine the pattern of neurosurgical lesions in children diagnosed in southwestern Nigeria and briefly address issues surrounding the practice of this aspect of pathology in Africa. We performed a retrospective review of histopathologic results of biopsies obtained from pediatric patients with neurosurgical lesions at the Department of Pathology, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria, between January 2001 and December 2011...
September 15, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27634962/serotonin-receptors-in-the-medulla-oblongata-of-the-human-fetus-and-infant-the-analytic-approach-of-the-international-safe-passage-study
#12
Robin L Haynes, Rebecca D Folkerth, David S Paterson, Kevin G Broadbelt, S Dan Zaharie, Richard H Hewlett, Johan J Dempers, Elsie Burger, Shabbir Wadee, Pawel Schubert, Colleen Wright, Mary Ann Sens, Laura Nelsen, Bradley B Randall, Hoa Tran, Elaine Geldenhuys, Amy J Elliott, Hein J Odendaal, Hannah C Kinney
The Safe Passage Study is an international, prospective study of approximately 12 000 pregnancies to determine the effects of prenatal alcohol exposure (PAE) upon stillbirth and the sudden infant death syndrome (SIDS). A key objective of the study is to elucidate adverse effects of PAE upon binding to serotonin (5-HT) 1A receptors in brainstem homeostatic networks postulated to be abnormal in unexplained stillbirth and/or SIDS. We undertook a feasibility assessment of 5-HT1A receptor binding using autoradiography in the medulla oblongata (6 nuclei in 27 cases)...
September 15, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27634961/molecular-and-cellular-responses-to-interleukin-4-treatment-in-a-rat-model-of-transient-ischemia
#13
Starlee Lively, Sarah Hutchings, Lyanne C Schlichter
Within hours after stroke, potentially cytotoxic pro-inflammatory mediators are elevated within the brain; thus, one potential therapeutic strategy is to reduce them and skew the brain toward an anti-inflammatory state. Because interleukin-4 (IL-4) treatment induces an anti-inflammatory, "alternative-activation" state in microglia and macrophages in vitro, we tested the hypothesis that early supplementation of the brain with IL-4 can shift it toward an anti-inflammatory state and reduce damage after transient focal ischemia...
September 15, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27634960/histopathologic-analysis-of-cerebral-autosomal-recessive-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy-carasil-a-report-of-a-new-genetically-confirmed-case-and-comparison-to-2-previous-cases
#14
Shinji Ito, Masaki Takao, Toshio Fukutake, Hiroyuki Hatsuta, Sayaka Funabe, Nobuo Ito, Yutaka Shimoe, Toshiro Niki, Imaharu Nakano, Masashi Fukayama, Shigeo Murayama
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a nonhypertensive hereditary cerebral small vessel disease that is caused by mutations in a single gene, HTRA1 The HTRA1 protein normally represses transforming growth factor-β (TGF-β) signaling and its mutations result in vascular changes. Ten homozygous, 1 compound heterozygous, and 1 homozygous frameshift mutation have been identified in the HTRA1 gene of patients with genetically confirmed CARASIL...
September 15, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27650403/in-this-issue
#15
(no author information available yet)
No abstract text is available yet for this article.
October 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27543120/chronic-traumatic-encephalopathy-pathology-in-multiple-system-atrophy
#16
Shunsuke Koga, Dennis W Dickson, Kevin F Bieniek
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder associated with repetitive traumatic brain injury. Multiple system atrophy (MSA) is a Parkinsonian disorder that can result in repetitive falls with associated head trauma. We hypothesized that patients with neurodegenerative disorders like MSA could develop CTE pathology. Therefore, we assessed CTE pathology in 139 MSA cases in our brain bank. Sections from convexity cerebral cortices were screened by immunohistochemistry with anti-phospho-tau antibody...
October 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27539476/protein-analysis-of-glioblastoma-primary-and-posttreatment-pairs-suggests-a-mesenchymal-shift-at-recurrence
#17
Matthew D Wood, Gerald F Reis, David E Reuss, Joanna J Phillips
Glioblastomas (GBM) are aggressive brain tumors that inevitably recur despite surgical resection, chemotherapy, and radiation. The degree to which recurrent GBM retains its initial immunophenotype is incompletely understood. We generated tissue microarrays of paired initial and posttreatment GBM (3 pairs positive and 17 negative for IDH1(R132H)) from the same patients and made comparisons in the IDH1(R132H)-negative group for immunohistochemical and gene expression differences between primary and recurrent tumors...
October 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27516117/tamoxifen-induces-cytotoxic-autophagy-in-glioblastoma
#18
Christopher D Graham, Niroop Kaza, Barbara J Klocke, G Yancey Gillespie, Lalita A Shevde, Steven L Carroll, Kevin A Roth
Glioblastomas (GBMs) are the most common and aggressive primary human malignant brain tumors. 4-Hydroxy tamoxifen (OHT) is an active metabolite of the tamoxifen (TMX) prodrug and a well-established estrogen receptor (ER) and estrogen-related receptor antagonist. A recent study from our laboratory demonstrated that OHT induced ER-independent malignant peripheral nerve sheath tumor (MPNST) cell death by autophagic degradation of the prosurvival protein Kirsten rat sarcoma viral oncogene homolog. Because both MPNST and GBM are glial in cell origin, we hypothesized that OHT could mediate similar effects in GBM...
October 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27516116/late-life-vascular-risk-factors-and-alzheimer-disease-neuropathology-in-individuals-with-normal-cognition
#19
Lilah M Besser, Michael L Alosco, Liliana Ramirez Gomez, Xiao-Hua Zhou, Ann C McKee, Robert A Stern, John Gunstad, Julie A Schneider, Helena Chui, Walter A Kukull
Vascular risk factors (VRFs) have been associated with clinically diagnosed Alzheimer disease (AD), but few studies have examined the association between VRF and AD neuropathology (ADNP) in cognitively normal individuals. We used longitudinal data from the National Alzheimer's Disease Center's Uniform Data Set and Neuropathology Data Set to examine the association between VRF and ADNP (moderate to frequent neuritic plaques; Braak stage III-VI) in those with normal cognition. Our sample included 53 participants with ADNP and 140 without ADNP...
October 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27612489/hippocampal-formation-maldevelopment-and-sudden-unexpected-death-across-the-pediatric-age-spectrum
#20
Hannah C Kinney, Annapurna H Poduri, Jane B Cryan, Robin L Haynes, Lisa Teot, Lynn A Sleeper, Ingrid A Holm, Gerald T Berry, Sanjay P Prabhu, Simon K Warfield, Catherine Brownstein, Harry S Abram, Michael Kruer, Walter L Kemp, Beata Hargitai, Joanne Gastrang, Othon J Mena, Elisabeth A Haas, Roya Dastjerdi, Dawna D Armstrong, Richard D Goldstein
Sudden infant death syndrome (SIDS) and sudden unexplained death in childhood (SUDC) are defined as sudden death in a child remaining unexplained despite autopsy and death scene investigation. They are distinguished from each other by age criteria, i.e. with SIDS under 1 year and SUDC over 1 year. Our separate studies of SIDS and SUDC provide evidence of shared hippocampal abnormalities, specifically focal dentate bilamination, a lesion classically associated with temporal lobe epilepsy, across the 2 groups...
September 9, 2016: Journal of Neuropathology and Experimental Neurology
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