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Journal of Neuropathology and Experimental Neurology

Melanie D Laarman, Ynte M Ruigrok, Renske C S Nierstrasz, Wim G M Spliet, Wim Van Hecke, Ale Algra, Gabriël J E Rinkel
Intracranial aneurysms (IAs) develop more often on bifurcations compared with the rest of the circle of Willis (CoW). We investigated histological differences between 2 high IA prevalence sites (anterior communicating artery [AcomA] and basilar tip) and 2 corresponding low IA prevalence sites (anterior cerebral artery [ACA] and basilar artery [BA]) using histological sections of 10 CoWs without IAs. Medial defect density in the AcomA was 0.24 medial defects/mm compared with 0.02 for the A1 part and 0.03 for the A2 part of the ACA...
May 6, 2019: Journal of Neuropathology and Experimental Neurology
Caroline Esmonde-White, Moein Yaqubi, Philippe A Bilodeau, Qiao Ling Cui, Florian Pernin, Catherine Larochelle, Mahtab Ghadiri, Yu Kang T Xu, Timothy E Kennedy, Jeffery Hall, Luke M Healy, Jack P Antel
Remyelination in the human CNS is ascribed to progenitor cells rather than previously myelinating oligodendrocytes (OLs). The ganglioside-recognizing antibody A2B5 has been used to isolate putative progenitor cells, whose in vitro features resemble cells labeled as "pre-oligodendrocytes." Here, we compare the transcriptional profiles of adult human brain-derived A2B5 antibody-selected cells (A+) after initial isolation (day in vitro (DIV1)) and after DIV6, with nonselected (A-) cells (mature OLs), with regard to their differentiation state and functional properties...
May 6, 2019: Journal of Neuropathology and Experimental Neurology
Rikke H Dahlrot, Pia Larsen, Henning B Boldt, Melissa S Kreutzfeldt, Steinbjørn Hansen, Jacob B Hjelmborg, Bjarne Winther Kristensen
The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes temozolomide-induced alkylation, thereby preventing DNA damage and cytotoxicity. We investigated the prognostic effect of different MGMT methylation levels on overall and progression-free survival in 327 patients with primary glioblastoma undergoing standard treatment. We obtained MGMT methylation level in 4 CpG sites using pyrosequencing. The association between MGMT methylation level and survival was investigated using Cox proportional hazards model and an extension to detect time-varying effects...
May 6, 2019: Journal of Neuropathology and Experimental Neurology
Navina L Chrobok, John G J M Bol, Micha M M Wilhelmus, Benjamin Drukarch, Anne-Marie van Dam
Leukocyte infiltration is an important pathological hallmark of multiple sclerosis (MS) and is therefore targeted by current MS therapies. The enzyme tissue transglutaminase (TG2) contributes to monocyte/macrophage migration and is present in MS lesions and could be a potential therapeutic target. We examined the cellular identity of TG2-expressing cells by immunohistochemistry in white matter lesions of 13 MS patients; 9 active and chronic active lesions from 4 patients were analyzed in detail. In these active MS lesions, TG2 is predominantly expressed in leukocytes (CD45+) but not in cells of the lymphocyte lineage, that is, T cells (CD3+) and B cells (CD20+)...
May 6, 2019: Journal of Neuropathology and Experimental Neurology
Leandro Castañeyra-Ruiz, Luis G Hernández-Abad, Emilia M Carmona-Calero, Agustín Castañeyra-Perdomo, Ibrahim González-Marrero
The choroid plexus (ChP) is involved in the production of cerebrospinal fluid (CSF) and is intimately related to CSF physiopathology. Aquaporin-1 (AQP1) is the water channel directly implicated in CSF production and a potential therapeutic target in the management of CSF circulation disorders. Pathologies that present ventriculomegaly are associated with defective CSF turnover and AQPs are involved in both the production and reabsorption of CSF. This work examines the levels of AQP1 and its dynamics in ventriculomegaly conditions such as congenital hydrocephalus (communicating and obstructive) or type II lissencephaly versus control...
April 30, 2019: Journal of Neuropathology and Experimental Neurology
Timothy E Richardson, Seema Patel, Jonathan Serrano, Adwait Amod Sathe, Elena V Daoud, Dwight Oliver, Elizabeth A Maher, Alejandra Madrigales, Bruce E Mickey, Timothy Taxter, George Jour, Charles L White, Jack M Raisanen, Chao Xing, Matija Snuderl, Kimmo J Hatanpaa
Glioblastoma (GBM), representing WHO grade IV astrocytoma, is a relatively common primary brain tumor in adults with an exceptionally dismal prognosis. With an incidence rate of over 10 000 cases in the United States annually, the median survival rate ranges from 10-15 months in IDH1/2-wildtype tumors and 24-31 months in IDH1/2-mutant tumors, with further variation depending on factors such as age, MGMT methylation status, and treatment regimen. We present a cohort of 4 patients, aged 37-60 at initial diagnosis, with IDH1-mutant GBMs that were associated with unusually long survival intervals after the initial diagnosis, currently ranging from 90 to 154 months (all still alive)...
April 29, 2019: Journal of Neuropathology and Experimental Neurology
Shelley L Forrest, Jillian J Kril, Stephanie Wagner, Selma Hönigschnabl, Angelika Reiner, Peter Fischer, Gabor G Kovacs
This study determined the prevalence of chronic traumatic encephalopathy (CTE) and cortical aging-related tau astrogliopathy (ARTAG) in a European community-based population (n = 310). The frontal, parietal, and temporal cortices, representing initial stages of CTE were assessed. No case fulfilling CTE consensus criteria was found. However, isolated astroglial or neuronal tau pathologies were recognized in the depths of cortical sulci (<2%). A single case (female, 85 years) without a history of traumatic brain injury (TBI) showed combined tau-immunoreactive features confined to frontal sulci without perivascular accumulation...
April 2, 2019: Journal of Neuropathology and Experimental Neurology
Yanqing Li, Dongyang Wang, Ya Li, Jiuling Zhu, Junli Zhao, Yanchun Deng, Emily J Rogalski, Eileen H Bigio, Alfred W Rademaker, Haibin Xia, Qinwen Mao
Progranulin (PGRN) plays critical roles in inflammation, tumorigenesis, and neurodegeneration. PGRN levels in blood and cerebrospinal fluid (CSF) are being increasingly investigated as potential biomarkers for these disorders. However, the value of CSF PGRN as a biomarker has been limited because currently available commercial enzyme-linked immunosorbent assay (ELISA) kits have suboptimal sensitivity for detecting CSF PGRN. In this study, pairs of monoclonal antibodies (MAbs) were first screened from eleven monoclonal antiPGRN antibodies using indirect ELISA, then a sandwich ELISA was established using the 2 optimized MAbs...
April 2, 2019: Journal of Neuropathology and Experimental Neurology
Pol Andrés-Benito, Mònica Povedano, Pascual Torres, Manuel Portero-Otín, Isidro Ferrer
Dyneins are major components of microtubules. Dynein assembly is modulated by a heterogeneous group of dynein axonemal assembly factors (DNAAFs). The present study analyzes dynein axonemal assembly factor 1 (DNAAF1) and leucine-rich repeat-containing protein 50 (LRRC50), the corresponding encoded protein, in lower motor neurons in spinal cord of sALS postmortem samples and hSOD1-G93A transgenic mice compared with controls. DNAAF1 mRNA is significantly reduced in the anterior horn in sALS, and LRRC50 immunoreactivity is significantly reduced in C-boutons of the remaining motor neurons of the anterior horn, dorsal nucleus of the vagus nerve, and hypoglossal nuclei at terminal stages of ALS...
April 2, 2019: Journal of Neuropathology and Experimental Neurology
Bruno P Meloni, Samantha M South, Daphne A Gill, Amber L Marriott, Robert A Déziel, Angela Jacques, David J Blacker, Neville W Knuckey
We have previously demonstrated that R18 and its d-enantiomer, R18D, are neuroprotective at 24 hours following intraluminal filament occlusion of the middle cerebral artery (MCAO) in the rat. This study examined R18 and R18D effectiveness in improving functional outcomes at up to 56 days poststroke following endothelin-1-induced MCAO. Peptides were administered intravenously at doses of 100, 300, or 1000 nmol/kg, 60 minutes after MCAO. Functional recovery poststroke was assessed using multiple forelimb placing tests and horizontal ladder test, and NA-1 (TAT-NR2B9c), a neuroprotective currently in phase 3 clinical stroke trials, was used as a benchmark...
March 19, 2019: Journal of Neuropathology and Experimental Neurology
Jovan C D Hasmatali, Jolly De Guzman, Ruiling Zhai, Lisa Yang, Nikki A McLean, Catherine Hutchinson, Jayne M Johnston, Vikram Misra, Valerie M K Verge
Luman/CREB3 is an important early retrograde axotomy signal regulating acute axon outgrowth in sensory neurons through the adaptive unfolded protein response. As the injury response is transcriptionally multiphasic, a spatiotemporal analysis of Luman/CREB3 localization in rat dorsal root ganglion (DRG) with unilateral L4-L6 spinal nerve injury was conducted to determine if Luman/CREB3 expression was similarly regulated. Biphasic alterations in Luman/CREB3 immunofluorescence and nuclear localization occurred in neurons ipsilateral to 1-hour, 1-day, 2-day, 4-day, and 1-week injury, with a largely parallel, but less avid response contralaterally...
March 12, 2019: Journal of Neuropathology and Experimental Neurology
Man Li, Liang Zeng, Shengwen Liu, Sean Dangelmajer, Ulf D Kahlert, Hao Huang, Yang Han, Xiaohui Chi, Mingxin Zhu, Ting Lei
Human mesenchymal stem cell-based tumor therapeutic gene delivery is regarded as a promising strategy for the treatment of glioblastoma (GBM). However, the efficiency of these stem cells to home to the target sites limits their potential curative effect and clinical application. In this work, we provide a novel pretreatment approach for enhancing the homing capacity of human adipose-derived mesenchymal stem cells (hAMSCs) for stem cell-based tumor gene delivery for GBM therapy. Pre-exposure of these stem cells to TGF-β resulted in enhanced homing ability to GBM through increasing CXC chemokine receptor 4 (CXCR4) expression, as evidenced by a diminishing homing capacity when inhibition of the TGF-β receptor II and CXCR4 was applied...
March 12, 2019: Journal of Neuropathology and Experimental Neurology
Colleen E D'Arcy, Ari Bitnun, Michael B Coulthart, Rolande D'Amour, Jeremy Friedman, J David Knox, Adam Rapoport, Snead Carter, Elysa Widjaja, Lili-Naz Hazrati, Gerard H Jansen
Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, fatal degenerative encephalopathy caused by a pathologically altered form of the prion protein (PrP). CJD is rare, with 1 and 2 cases per million per year reported in the general population, mostly in individuals over 50 years of age. It is almost unknown in the pediatric population. Sporadic CJD with unusually long survival (sCJD-LS), an unusual clinicopathological variant of CJD, has been described mostly in Japanese patients. We present here the first case report of pediatric CJD-LS occurring sporadically in a teenage girl of European descent, with initially rapid neurocognitive decline followed by a prolonged (∼10 years) clinical course...
March 11, 2019: Journal of Neuropathology and Experimental Neurology
Pengcheng Han, Cynthia T Welsh, Michael T Smith, Robert E Schmidt, Steven L Carroll
Focal cortical dysplasia (FCD) is a common histopathologic finding in cortical specimens resected for refractory epilepsy. GABAergic neuronal abnormalities and K-Cl cotransporter type 2 (KCC2) immaturity may be contributing factors for FCD-related epilepsy. We examined surgical specimens from 12 cases diagnosed with FCD, and brain tissues without developmental abnormality obtained from 6 autopsy cases. We found that GABAergic neuronal density was abnormal in FCD with 2 distinct patterns. In 7 of 12 (58%) FCD subjects, the GABAergic neuron density in dysplastic regions and in neighboring nondysplastic regions was equally reduced, hence we call this a "broad pattern...
March 11, 2019: Journal of Neuropathology and Experimental Neurology
Patricia Trevisan, Carla Graziadio, Dayane Bohn Koshiyama Rodrigues, Rafael Fabiano Machado Rosa, Fabiano Pasqualotto Soares, Valentina Oliveira Provenzi, Ceres Andréia Vieira de Oliveira, Giorgio Adriano Paskulin, Marileila Varella-Garcia, Paulo Ricardo Gazzola Zen
We investigated 113 adult Brazilian patients with glioblastoma (GBM) for comparison with patients from distinct geographical areas and evaluation of suitability for novel targeted therapies. Patients were assessed for clinical features and tumor genomic characteristics such as ROS1 and NTRK1 rearrangements, KIT, PDGFRA, and KDR amplification, and RB1 deletion using multicolor fluorescence in situ hybridization. The majority of patients were male (53%), over 40 years (94%), with tumor located in single site (64%), in the right cerebral hemisphere (60%), and underwent partial resection (71%); 14% presented complications after surgery...
March 6, 2019: Journal of Neuropathology and Experimental Neurology
Gabrielle A Yeaney, Daniel J Brat
World Health Organization (WHO) central nervous system tumor classification represents the primary source of updates on diagnostic classes, grades, and criteria. However, recent and ongoing advances in molecular pathogenesis warrant more rapid integration into clinical practice between WHO updates. To accomplish this, the consortium to inform molecular and practical approaches to CNS tumor taxonomy-not official WHO (cIMPACT-NOW) was established in 2016. Since then, cIMPACT-NOW has convened 3 separate working committees to address classification and grading questions and challenges...
March 4, 2019: Journal of Neuropathology and Experimental Neurology
Vanda Téglási, Dániel T Csűry, Katalin Dezső, Edina Bugyik, Vanessza Szabó, Zoltán Szállási, Sándor Paku, Lilla Reiniger
The impact of growth pattern on the distribution of connective tissue and on the vascularization of brain metastases (40 colon, lung and breast carcinoma samples) was analyzed. Most of the cases showed either a "pushing-type" (18/40, mostly colon and lung carcinomas) or a "papillary-type" (19/40, mostly breast carcinomas) growth pattern. There was a striking difference in the growth pattern and vascularization of colon/lung versus breast carcinoma metastases. Pushing-type brain metastases incorporated fewer vessels and accumulated more collagen in the adjacent brain parenchyma, whereas papillary-type brain metastases incorporated more vessels and accumulated collagen in the center of the tumor...
February 28, 2019: Journal of Neuropathology and Experimental Neurology
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No abstract text is available yet for this article.
June 1, 2019: Journal of Neuropathology and Experimental Neurology
Svenja Kiljan, Marloes Prins, Bart M Baselmans, John G J M Bol, Geert J Schenk, Anne-Marie van Dam
Cognitive dysfunction occurs frequently in multiple sclerosis (MS). Research suggests that hippocampal lesions and GABAergic neurotransmitter changes contribute to cognitive dysfunction. In the present study, we aim to determine the cellular changes in GABAergic expression in MS hippocampus related to inflammation and demyelination. To this end, the presence and inflammatory activity of demyelinating lesions was determined by immunohistochemistry in human postmortem hippocampal tissue of 15 MS patients and 9 control subjects...
June 1, 2019: Journal of Neuropathology and Experimental Neurology
Jian-Qiang Lu, Adnan Mubaraki, Chuanzhu Yan, John Provias, Mark A Tarnopolsky
Mitochondrial diseases (MIDs) involve peripheral nerves and skeletal muscle, but the prevalence of mitochondrial neuropathy is still unclear. Mitochondrial neuropathy has been found to correlate with muscle weakness that may be due to myopathic and/or neurogenic myopathy in patients with MIDs. We examined vastus lateralis muscle biopsies of 58 consecutive patients with mitochondrial myopathy (MM), compared with 204 consecutive non-MM patients. Muscle fiber denervation atrophy was found in 39/58 (67%) of MM patients, significantly more than 41/204 (20%) of non-MM patients and 20/58 (34%) of clinically diagnosed neuropathy...
June 1, 2019: Journal of Neuropathology and Experimental Neurology
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