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.

Feasibility Study: Comparison of Frontal Cortex Needle Core Versus Open Biopsy for Detection of Characteristic Proteinopathies of Neurodegenerative Diseases
This study shows that the presence and densities of the most common molecular pathologies may be histopathologically assessed in simulated frontal cortex needle biopsies, with accuracy very close to that obtained by open cortical biopsy. An accurate estimation of the morbidity and mortality risk associated with cortical needle core biopsy will require specifically designed clinical trials in appropriate subjects. (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - August 21, 2015 Category: Neurology Tags: Original Articles Source Type: research

Quantitative Real-Time Quaking-Induced Conversion Allows Monitoring of Disease-Modifying Therapy in the Urine of Prion-Infected Mice
Abstract: Prion diseases are fatal neurodegenerative diseases characterized by accumulation of the pathogenic prion protein PrPSc in the brain. We established quantitative real-time quaking-induced conversion for the measurement of minute amounts of PrPSc in body fluids such as urine. Using this approach, we monitored the efficacy of antiprion therapy by quantifying the seeding activity of PrPSc from the brain and urine of mice after prion infection. We found that the aggregation inhibitor anle138b decreased the levels of PrPSc in the brain and urine. Importantly, variations of PrPSc levels in the urine closely corresponde...
Source: Journal of Neuropathology and Experimental Neurology - August 21, 2015 Category: Neurology Tags: Original Articles Source Type: research

Detection and Quantification of β-Amyloid, Pyroglutamyl Aβ, and Tau in Aged Canines
This study provides the first investigation of pyroglutamyl Aβ in comparison with total Aβ (as shown by Aβ8–17 immunoreactivity) in dogs of different breeds, sizes, and ages. Our results indicate that canine cognitive dysfunction syndrome is relatively common among aged canines, thereby emphasizing the relevance of such populations to translational Alzheimer disease research. (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - August 21, 2015 Category: Neurology Tags: Original Articles Source Type: research

Human Neuroma-in-Continuity Contains Focal Deficits in Myelination
Abstract: Functional recovery does not occur in 10% of patients with neonatal brachial plexus palsy. In these patients, resection of a neuroma-in-continuity (NIC) and surgical nerve reconstruction are required. The formation of a NIC seems to prohibit functional recovery, but the underlying biologic mechanisms for this failure are poorly understood. We systematically analyzed a large series of NIC tissue samples from 17 neonatal and 3 adult patients using an array of immunohistochemical techniques. In a large proportion of patients (74%), the NIC contained multiple focal globular areas with markedly diminished myelination....
Source: Journal of Neuropathology and Experimental Neurology - August 21, 2015 Category: Neurology Tags: Original Articles Source Type: research

Pharmacologic Wnt Inhibition Reduces Proliferation, Survival, and Clonogenicity of Glioblastoma Cells
Abstract: Wingless (Wnt) signaling is an important pathway in gliomagenesis and in the growth of stem-like glioma cells. Using immunohistochemistry to assess the translocation of β-catenin protein, we identified intranuclear staining suggesting Wnt pathway activation in 8 of 43 surgical samples (19%) from adult patients with glioblastoma and in 9 of 30 surgical samples (30%) from pediatric patients with glioblastoma. Wnt activity, evidenced by nuclear β-catenin in our cohort and high expression of its target AXIN2 (axis inhibitor protein 2) in published glioma datasets, was associated with shorter patient survival, altho...
Source: Journal of Neuropathology and Experimental Neurology - August 21, 2015 Category: Neurology Tags: Original Articles Source Type: research

Prion Disease Induces Alzheimer Disease–Like Neuropathologic Changes
We examined the brains of 266 patients with prion disease (PrionD) and found that 46 patients (17%) had Alzheimer disease (AD)–like changes. To explore potential mechanistic links between PrionD and AD, we exposed human brain aggregates (BrnAggs) to a brain homogenate from a patient with sporadic Creutzfeldt-Jakob disease and found that neurons in human BrnAggs produced many β-amyloid (Aβ; Aβ42) inclusions, whereas uninfected control-exposed human BrnAggs did not. Western blot analysis of 20 pooled Creutzfeldt-Jakob disease–infected BrnAggs verified Aβ42 levels higher than those in controls. We next examined the CA...
Source: Journal of Neuropathology and Experimental Neurology - August 21, 2015 Category: Neurology Tags: Original Articles Source Type: research

BRAF Fusion Analysis in Pilocytic Astrocytomas: KIAA1549-BRAF 15-9 Fusions Are More Frequent in the Midline Than Within the Cerebellum
Abstract: Pilocytic astrocytomas (PAs) are increasingly tested for KIAA1549-BRAF fusions. We used reverse transcription polymerase chain reaction for the 3 most common KIAA1549-BRAF fusions, together with BRAF V600E and histone H3.3 K27M analyses to identify relationships of these molecular characteristics with clinical features in a cohort of 32 PA patients. In this group, the overall BRAF fusion detection rate was 24 (75%). Ten (42%) of the 24 had the 16-9 fusion, 8 (33%) had only the 15-9 fusion, and 1 (4%) of the patients had only the 16-11 fusion. In the PAs with only the 15-9 fusion, 1 PA was in the cerebellum and 7 ...
Source: Journal of Neuropathology and Experimental Neurology - August 21, 2015 Category: Neurology Tags: Original Articles Source Type: research

Differentiation of Donor-Derived Cells Into Microglia After Umbilical Cord Blood Stem Cell Transplantation
Abstract: Recent studies have indicated that microglia originate from immature progenitors in the yolk sac. After birth, microglial populations are maintained under normal conditions via self-renewal without the need to recruit monocyte-derived microglial precursors. Peripheral cell invasion of the brain parenchyma can only occur with disruption of the blood-brain barrier. Here, we report an autopsy case of an umbilical cord blood transplant recipient in whom cells derived from the donor blood differentiated into ramified microglia in the recipient brain parenchyma. Although the blood-brain barrier and glia limitans seemed...
Source: Journal of Neuropathology and Experimental Neurology - August 21, 2015 Category: Neurology Tags: Brief Report Source Type: research

In This Issue
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - August 21, 2015 Category: Neurology Tags: In This Issue Source Type: research

Mary Ambler, MD 1932–2015
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - July 22, 2015 Category: Neurology Tags: In Memoriam Source Type: research

Stanley Maynard Aronson, MD 1922–2015
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - July 22, 2015 Category: Neurology Tags: In Memoriam Source Type: research

Early Neurodegeneration in the Brain of a Child Without Functional PKR-like Endoplasmic Reticulum Kinase
We report the first detailed examination of the brain of a patient with Wolcott-Rallison syndrome. Wolcott-Rallison syndrome is an extremely rare clinical manifestation of a lack of protein kinase R–like endoplasmic reticulum kinase (PERK) function caused by mutations in the PERK gene EIF2AK3. Protein kinase R–like endoplasmic reticulum kinase is thought to play a significant pathogenetic role in several neurodegenerative diseases, including Alzheimer disease, other tauopathies, and Parkinson disease. The brain of a male patient aged 4 years 7 months showed pathologic and immunohistochemical evidence that the absence o...
Source: Journal of Neuropathology and Experimental Neurology - July 22, 2015 Category: Neurology Tags: Original Articles Source Type: research

Sur1-Trpm4 Cation Channel Expression in Human Cerebral Infarcts
We examined Trpm4 expression in postmortem brain specimens from 15 patients who died within the first 31 days of the onset of focal cerebral ischemia. We found increased Trpm4 protein expression in all cases using immunohistochemistry; transcriptional upregulation was confirmed using in situ hybridization of Trpm4 messenger RNA. Transient receptor potential melastatin 4 colocalized and coassociated with Sur1 within ischemic endothelial cells and neurons. Coexpression of Sur1 and Trpm4 in necrotic endothelial cells was also associated with vasogenic edema indicated by upregulated perivascular tumor necrosis factor, extravas...
Source: Journal of Neuropathology and Experimental Neurology - July 22, 2015 Category: Neurology Tags: Original Articles Source Type: research

Neuronal Regulation of Neuroprotective Microglial Apolipoprotein E Secretion in Rat In Vitro Models of Brain Pathophysiology
Abstract: Apolipoprotein E (ApoE) is mainly secreted by glial cells and is involved in many brain functions, including neuronal plasticity, β-amyloid clearance, and neuroprotection. Microglia—the main immune cells of the brain—are one source of ApoE, but little is known about the physiologic regulation of microglial ApoE secretion by neurons and whether this release changes under inflammatory or neurodegenerative conditions. Using rat primary neural cell cultures, we show that microglia release ApoE through a Golgi-mediated secretion pathway and that ApoE progressively accumulates in neuroprotective microglia-conditio...
Source: Journal of Neuropathology and Experimental Neurology - July 22, 2015 Category: Neurology Tags: Original Articles Source Type: research

Evidence for Epigenetic Regulation of Gene Expression and Function in Chronic Experimental Diabetic Neuropathy
Abstract: Diabetic polyneuropathy (DPN) is a common but irreversible neurodegenerative complication of diabetes mellitus. Here we show that features of sensory neuron damage in mice with chronic DPN may have altered epigenetic micro RNA (miRNA) transcriptional control. We profiled sensory neuron messenger RNA and miRNA profiles in mice with type I diabetes mellitus and findings of DPN. Diabetic sensory dorsal root ganglia neurons showed a pattern of altered messenger RNA profiles associated with upregulated cytoplasmic sites of miRNA-mediated messenger RNA processing (GW/P bodies). Dorsal root ganglia miRNA microarray iden...
Source: Journal of Neuropathology and Experimental Neurology - July 22, 2015 Category: Neurology Tags: Original Articles Source Type: research