Journal of Neuropathology and Experimental Neurology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Lack of Major Histocompatibility Complex Class I Upregulation and Restrictive Infection by JC Virus Hamper Detection of Neurons by T Lymphocytes in the Central Nervous System
Abstract: The human polyomavirus JC (JCV) infects glial cells in immunosuppressed individuals, leading to progressive multifocal leukoencephalopathy. Polyomavirus JC can also infect neurons in patients with JCV granule cell neuronopathy and JCV encephalopathy. CD8-positive T cells play a crucial role in viral containment and outcome in progressive multifocal leukoencephalopathy, but whether CD8-positive T cells can also recognize JCV-infected neurons is unclear. We used immunohistochemistry to determine the prevalence of T cells in neuron-rich areas of archival brain samples from 77 patients with JCV CNS infections and 94 ...
Source: Journal of Neuropathology and Experimental Neurology - July 22, 2015 Category: Neurology Tags: Original Articles Source Type: research

Disrupting NOTCH Slows Diffuse Intrinsic Pontine Glioma Growth, Enhances Radiation Sensitivity, and Shows Combinatorial Efficacy With Bromodomain Inhibition
Abstract: NOTCH regulates stem cells during normal development and stemlike cells in cancer, but the roles of NOTCH in the lethal pediatric brain tumor diffuse intrinsic pontine glioma (DIPG) remain unknown. Because DIPGs express stem cell factors such as SOX2 and MYCN, we hypothesized that NOTCH activity would be critical for DIPG growth. We determined that primary DIPGs expressed high levels of NOTCH receptors, ligands, and downstream effectors. Treatment of the DIPG cell lines JHH-DIPG1 and SF7761 with the γ-secretase inhibitor MRK003 suppressed the level of the NOTCH effectors HES1, HES4, and HES5; inhibited DIPG grow...
Source: Journal of Neuropathology and Experimental Neurology - July 22, 2015 Category: Neurology Tags: Original Articles Source Type: research

Human Parechovirus 3 Meningitis and Fatal Leukoencephalopathy
We report pathologic findings in 2 autopsy cases of infants with active HPeV3 infection. Both children were born approximately 1 month premature and were neurologically intact but, after a few weeks, developed seizures and radiologic evidence of white matter lesions. Neuropathologic examination demonstrated classic severe periventricular leukomalacia in the absence of an immune response. Human parechovirus 3 sequences were identified in RNA extracted from CSF, sera, and tissues. Human parechovirus 3 in situ hybridization detection of infected cells was limited to meninges and associated blood vessels in addition to smooth ...
Source: Journal of Neuropathology and Experimental Neurology - July 22, 2015 Category: Neurology Tags: Original Articles Source Type: research

Remyelination After Cuprizone-Induced Demyelination Is Accelerated in Juvenile Mice
Abstract: Remyelination capacity decreases with age in adult mice, but data comparing remyelination capacity after toxic demyelination in developing mice versus adult mice are not available. We treated 3-week-old and adult C57BL/6 mice with cuprizone for 1 to 5 weeks and studied demyelination/remyelination and cellular reactions in the corpus callosum and motor cortex by histology, immunohistochemistry, and electron microscopy. We compared results between the 2 treated groups and age-matched controls. In juvenile mice, significant demyelination was detectable in the corpus callosum on Week 2 and in the motor cortex on Week...
Source: Journal of Neuropathology and Experimental Neurology - July 22, 2015 Category: Neurology Tags: Original Articles Source Type: research

August In This Issue
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - July 22, 2015 Category: Neurology Tags: In This Issue Source Type: research

KIAA1549: BRAF Gene Fusion and FGFR1 Hotspot Mutations Are Prognostic Factors in Pilocytic Astrocytomas
Abstract: Up to 20% of patients with pilocytic astrocytoma (PA) experience a poor outcome. BRAF alterations and Fibroblast growth factor receptor 1 (FGFR1) point mutations are key molecular alterations in Pas, but their clinical implications are not established. We aimed to determine the frequency and prognostic role of these alterations in a cohort of 69 patients with PAs. We assessed KIAA1549:BRAF fusion by fluorescence in situ hybridization and BRAF (exon 15) mutations by capillary sequencing. In addition, FGFR1 expression was analyzed using immunohistochemistry, and this was compared with gene amplification and hotspot...
Source: Journal of Neuropathology and Experimental Neurology - June 17, 2015 Category: Neurology Tags: Original Articles Source Type: research

Overexpression and Nucleolar Localization of γ-Tubulin Small Complex Proteins GCP2 and GCP3 in Glioblastoma
Abstract: The expression, cellular distribution, and subcellular sorting of the microtubule (MT)-nucleating γ-tubulin small complex (γTuSC) proteins, GCP2 and GCP3, were studied in human glioblastoma cell lines and in clinical tissue samples representing all histologic grades of adult diffuse astrocytic gliomas (n = 54). Quantitative real-time polymerase chain reaction revealed a significant increase in the expression of GCP2 and GCP3 transcripts in glioblastoma cells versus normal human astrocytes; these were associated with higher amounts of both γTuSC proteins. GCP2 and GCP3 were concentrated in the centrosomes in in...
Source: Journal of Neuropathology and Experimental Neurology - June 17, 2015 Category: Neurology Tags: Original Articles Source Type: research

Targeting Hypoxia-Inducible Factor 1α in a New Orthotopic Model of Glioblastoma Recapitulating the Hypoxic Tumor Microenvironment
We present a new GBM model, MGG123, which was established from a recurrent human GBM. Orthotopic xenografting of stem-like MGG123 cells reproducibly generated lethal tumors that were characterized by foci of palisading necrosis, hypervascularity, and robust stem cell marker expression. Perinecrotic neoplastic cells distinctively express HIF-1α and are proliferative in both xenografts and the patient tissue. The xenografts contain scattered hypoxic foci that were consistently greater than 50 μm distant from blood vessels, indicating intratumoral heterogeneity of oxygenation. Hypoxia enhanced HIF-1α expression in cultured...
Source: Journal of Neuropathology and Experimental Neurology - June 17, 2015 Category: Neurology Tags: Original Articles Source Type: research

Activation of Yes-Associated Protein in Low-Grade Meningiomas Is Regulated by Merlin, Cell Density, and Extracellular Matrix Stiffness
Abstract: The NF2 gene product Merlin is a protein containing ezrin, radixin, and moesin domains; it is a member of the 4.1 protein superfamily associated with the membrane cytoskeleton and also interacts with cell surface molecules. The mammalian Hippo cascade, a downstream signaling cascade of merlin, inactivates the Yes-associated protein (YAP). Yes-associated protein is activated by loss of the NF2 gene and functions as an oncogene in meningioma cells; however, the factors controlling YAP expression, phosphorylation, and subcellular localization in meningiomas have not been fully elucidated. Here, we demonstrate that m...
Source: Journal of Neuropathology and Experimental Neurology - June 17, 2015 Category: Neurology Tags: Original Articles Source Type: research

Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations
We describe 2 sisters with novel compound heterozygous RARS2 mutations who presented perinatally with neurologic features typical of PCH6 but with additional features including cardiomyopathy, hydrops, and pulmonary hypoplasia and who died at 1 day and 14 days of age. Magnetic resonance imaging findings included marked cerebellar hypoplasia, gyral immaturity, punctate lesions in cerebral white matter, and unfused deep cerebral grey matter. Enzyme histochemistry of postmortem tissues revealed a near-global cytochrome c oxidase-deficiency; assessment of respiratory chain enzyme activities confirmed severe deficiencies involv...
Source: Journal of Neuropathology and Experimental Neurology - June 17, 2015 Category: Neurology Tags: Original Articles Source Type: research

Cerebrospinal Fluid Particles in Alzheimer Disease and Parkinson Disease
Abstract: Human cerebrospinal fluid (CSF) contains diverse lipid particles, including lipoproteins that are distinct from their plasma counterparts and contain apolipoprotein (apo) E isoforms, apoJ, and apoAI, and extracellular vesicles, which can be detected by annexin V binding. The aim of this study was to develop a method to quantify CSF particles and evaluate their relationship to aging and neurodegenerative diseases. We used a flow cytometric assay to detect annexin V-, apoE-, apoAI-, apoJ-, and amyloid (A) β42-positive particles in CSF from 131 research volunteers who were neurologically normal or had mild cognitiv...
Source: Journal of Neuropathology and Experimental Neurology - June 17, 2015 Category: Neurology Tags: Original Articles Source Type: research

Cell Junction Pathology of Neural Stem Cells Is Associated With Ventricular Zone Disruption, Hydrocephalus, and Abnormal Neurogenesis
Abstract: Fetal-onset hydrocephalus affects 1 to 3 per 1,000 live births. It is not only a disorder of cerebrospinal fluid dynamics but also a brain disorder that corrective surgery does not ameliorate. We hypothesized that cell junction abnormalities of neural stem cells (NSCs) lead to the inseparable phenomena of fetal-onset hydrocephalus and abnormal neurogenesis. We used bromodeoxyuridine labeling, immunocytochemistry, electron microscopy, and cell culture to study the telencephalon of hydrocephalic HTx rats and correlated our findings with those in human hydrocephalic and nonhydrocephalic human fetal brains (n = 12 ea...
Source: Journal of Neuropathology and Experimental Neurology - June 17, 2015 Category: Neurology Tags: Original Articles Source Type: research

Hippocampal Sclerosis of Aging Can Be Segmental: Two Cases and Review of the Literature
Abstract: Hippocampal sclerosis of aging (HS-Aging) is a neurodegenerative disease that mimics Alzheimer disease (AD) clinically and has a prevalence rivaling AD in advanced age. Whereas clinical biomarkers are not yet optimized, HS-Aging has distinctive pathological features that distinguish it from other diseases with “hippocampal sclerosis” pathology, such as epilepsy, cerebrovascular perturbations, and frontotemporal lobar degeneration. By definition, HS-Aging brains show neuronal cell loss and gliosis in the hippocampal formation out of proportion to AD-type pathology; it is strongly associated with aberrant TDP-4...
Source: Journal of Neuropathology and Experimental Neurology - June 17, 2015 Category: Neurology Tags: Review Source Type: research

In This Issue
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - June 17, 2015 Category: Neurology Tags: In This Issue Source Type: research

American Association of Neuropathologists, Inc. Abstracts of the 91st Annual Meeting June 11–14, 2015 Denver, CO
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - May 20, 2015 Category: Neurology Tags: Abstracts Source Type: research