Combinatorial Therapy With Tamoxifen and Trifluoperazine Effectively Inhibits Malignant Peripheral Nerve Sheath Tumor Growth by Targeting Complementary Signaling Cascades
AbstractChemotherapeutic agents effective against malignant peripheral nerve sheath tumors (MPNSTs) are urgently needed. We recently found that tamoxifen potently impedes xenograft growth. In vitro, tamoxifen inhibits MPNST proliferation and survival in an estrogen receptor–independent manner; these effects are phenocopied by the calmodulin inhibitor trifluoperazine. The present study was performed to establish the mechanism of action of tamoxifen in vivo and optimize its therapeutic effectiveness. To determine if tamoxifen has estrogen receptor–dependent effects in vivo, we grafted MPNST cells in castrated and ovariec...
Source: Journal of Neuropathology and Experimental Neurology - October 24, 2014 Category: Neurology Tags: Original Articles Source Type: research

How Stemlike Are Sphere Cultures From Long-term Cancer Cell Lines? Lessons From Mouse Glioma Models
AbstractCancer stem cells may mediate therapy resistance and recurrence in various types of cancer, including glioblastoma. Cancer stemlike cells can be isolated from long-term cancer cell lines, including glioma lines. Using sphere formation as a model for cancer cell stemness in vitro, we derived sphere cultures from SMA-497, SMA-540, SMA-560, and GL-261 glioma cells. Gene expression and proteomics profiling demonstrated that sphere cultures uniformly showed an elevated expression of stemness-associated genes, notably including CD44. Differences in neural lineage marker expression between nonsphere and sphere cultures we...
Source: Journal of Neuropathology and Experimental Neurology - October 24, 2014 Category: Neurology Tags: Original Articles Source Type: research

Alterations in Tight Junction Protein and IgG Permeability Accompany Leukocyte Extravasation Across the Choroid Plexus During Neuroinflammation
AbstractThe choroid plexus (CP) is considered to be a point of leukocyte entry into the CNS during normal immune surveillance and in neuroinflammatory diseases. The structural and functional alterations within the CP that support this migration are not understood. We used quantitative, high-resolution, 3-dimensional (3-D) fluorescence imaging to analyze CP alterations associated with inflammatory responses in C57/Bl6 mice after the induction of experimental autoimmune encephalomyelitis by immunization with myelin oligodendrocyte glycoprotein (MOG) and complete Freund adjuvant/pertussis toxin (MOG-CFA/PTX) or adjuvants alon...
Source: Journal of Neuropathology and Experimental Neurology - October 24, 2014 Category: Neurology Tags: Original Articles Source Type: research

Bortezomib Sensitizes Primary Meningioma Cells to TRAIL-Induced Apoptosis by Enhancing Formation of the Death-Inducing Signaling Complex
AbstractA meningioma is the most common primary intracranial tumor in adults. Here, we investigated the therapeutic potential of the tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) in 37 meningiomas. Freshly isolated primary meningioma cells were treated with TRAIL with or without different sensitizing protocols, and apoptotic cell death was then quantified. Mechanisms of TRAIL sensitization were determined by a combination of Western blotting, flow cytometry, receptor complex immunoprecipitation, and siRNA-mediated knockdown experiments. Tumor necrosis factor–related apoptosis-inducing ligand receptor ...
Source: Journal of Neuropathology and Experimental Neurology - October 24, 2014 Category: Neurology Tags: Original Articles Source Type: research

Blood-Brain Barrier Dysfunction and Cerebral Small Vessel Disease (Arteriolosclerosis) in Brains of Older People
AbstractThe blood-brain barrier protects brain tissue from potentially harmful plasma components. Small vessel disease (SVD; also termed arteriolosclerosis) is common in the brains of older people and is associated with lacunar infarcts, leukoaraiosis, and vascular dementia. To determine whether plasma extravasation is associated with SVD, we immunolabeled the plasma proteins fibrinogen and immunoglobulin G, which are assumed to reflect blood-brain barrier dysfunction, in deep gray matter (DGM; anterior caudate-putamen) and deep subcortical white matter (DWM) in the brains of a well-characterized cohort of donated brains w...
Source: Journal of Neuropathology and Experimental Neurology - October 24, 2014 Category: Neurology Tags: Original Articles Source Type: research

Neuropathologic Features of Pontocerebellar Hypoplasia Type 6
We report 3 siblings who were born to nonconsanguineous parents, were hypotonic at birth, developed seizures, had repeated apneic spells, and died within 2 months of life. Neuroimaging showed that all had profound cerebellar hypoplasia and simplified cortical gyration. Genetic analysis by whole-exome sequencing demonstrated compound heterozygous mutations in the mitochondrial arginyl transfer RNA synthetase gene RARS2, indicating that the children had pontocerebellar hypoplasia type 6. Autopsies on the younger twin siblings revealed small and immature cerebella at an approximate developmental age of less than 18 weeks. The...
Source: Journal of Neuropathology and Experimental Neurology - October 24, 2014 Category: Neurology Tags: Original Articles Source Type: research

Enterovirus 71 Can Directly Infect the Brainstem via Cranial Nerves and Infection Can Be Ameliorated by Passive Immunization
AbstractEnterovirus 71 (EV71)–associated hand, foot, and mouth disease may be complicated by encephalomyelitis. We investigated EV71 brainstem infection and whether this infection could be ameliorated by passive immunization in a mouse model. Enterovirus 71 was injected into unilateral jaw/facial muscles of 2-week-old mice, and hyperimmune sera were given before or after infection. Harvested tissues were studied by light microscopy, immunohistochemistry, in situ hybridization, and viral titration. In unimmunized mice, viral antigen and RNA were detected within 24 hours after infection only in ipsilateral cranial nerves, ...
Source: Journal of Neuropathology and Experimental Neurology - October 24, 2014 Category: Neurology Tags: Original Articles Source Type: research

Cytomegalovirus and Glioblastoma: A Review of Evidence for Their Association and Indications for Testing and Treatment
AbstractGlioblastoma is the most common and most fatal primary malignant brain tumor in adults. Despite progress in characterizing the genetic and molecular mechanisms of glioblastomas, advances in treatment that translate into substantial improvement in prognosis have yet to be realized. A role for cytomegalovirus in glioblastoma pathogenesis was proposed more than a decade ago and has generated considerable debate as a possible therapeutic target. Independent groups have had variable success in detecting cytomegalovirus infection in tumor cells; the overall consensus is that very low levels of viral proteins and nucleic ...
Source: Journal of Neuropathology and Experimental Neurology - October 24, 2014 Category: Neurology Tags: Review Article Source Type: research

In This Issue
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - October 24, 2014 Category: Neurology Tags: In This Issue Source Type: research

Escourolle and Poirier’s Manual of Basic Neuropathology, Fifth Edition
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - October 1, 2014 Category: Neurology Tags: Book Review Source Type: research

David Emery Wolfe, MD January 3, 1933–June 3, 2014
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - October 1, 2014 Category: Neurology Tags: In Memoriam Source Type: research

2014 Award Recipients—Floyd Gilles, MD and Françoise Gray, MD, PhD
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - October 1, 2014 Category: Neurology Tags: Meritorious Awards Source Type: research

Hypoxia-Inducible Factor 1α Mediates Neuroprotection of Hypoxic Postconditioning Against Global Cerebral Ischemia
AbstractHypoxia administered after transient global cerebral ischemia (tGCI) has been shown to induce neuroprotection in adult rats, but the underlying mechanisms for this protection are unclear. Here, we tested the hypothesis that hypoxic postconditioning (HPC) induces neuroprotection through upregulation of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), and that this involves phosphatidylinositol-3-kinase (PI3K), p38 mitogen–activated protein kinase (p38 MAPK), and mitogen-activated protein kinase/extracellular signal–regulated kinase kinase (MEK) pathways. The expression of HIF...
Source: Journal of Neuropathology and Experimental Neurology - October 1, 2014 Category: Neurology Tags: Original Articles Source Type: research

Aberrant Production of Tenascin-C in Globoid Cell Leukodystrophy Alters Psychosine-Induced Microglial Functions
AbstractGloboid cell leukodystrophy (GLD), or Krabbe disease, is a rare and often fatal demyelinating disease caused by mutations in the galactocerebrosidase (galc) gene that result in accumulation of galactosylsphingosine (psychosine). We recently reported that the extracellular matrix (ECM) protease, matrix metalloproteinase-3, is elevated in GLD and that it regulates psychosine-induced microglial activation. Here, we examined central nervous system ECM component expression in human GLD patients and in the twitcher mouse model of GLD using immunohistochemistry. The influence of ECM proteins on primary murine microglial r...
Source: Journal of Neuropathology and Experimental Neurology - October 1, 2014 Category: Neurology Tags: Original Articles Source Type: research

Lysophosphatidylcholine and Amide as Metabolites for Detecting Alzheimer Disease Using Ultrahigh-Performance Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry–Based Metabonomics
AbstractAlzheimer disease (AD) can be diagnosed by clinical and neuropsychologic tests and at autopsy, but there are no simple effective diagnostic methods for detecting biomarkers in patients at early stages of cognitive impairment. Early metabolic alterations that may facilitate AD diagnosis have not been thoroughly explored. We applied a nontargeted metabonomic approach using ultrahigh-performance liquid chromatography–quadrupole time-of-flight mass spectrometry to analyze serum and urine samples from 46 patients with AD and 36 healthy controls. Metabolite profiles were processed using multivariate analysis to identif...
Source: Journal of Neuropathology and Experimental Neurology - October 1, 2014 Category: Neurology Tags: Original Articles Source Type: research