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.

Friedreich Ataxia: Failure of GABA-ergic and Glycinergic Synaptic Transmission in the Dentate Nucleus
AbstractAtrophy of large neurons in the dentate nucleus (DN) is an important pathologic correlate of neurologic disability in patients with Friedreich ataxia (FA). Thinning of the DN was quantified in 29 autopsy cases of FA and 2 carriers by measuring the thickness of the gray matter ribbon on stains with anti–glutamic acid decarboxylase, the rate-limiting enzyme in the biosynthesis of γ-amino-butyric acid (GABA). The DN was thinner than normal in all cases of FA, and atrophy correlated inversely with disease duration but not with age at onset or length of the homozygous guanine-adenine-adenine trinucleotide expansions....
Source: Journal of Neuropathology and Experimental Neurology - January 16, 2015 Category: Neurology Tags: Original Articles Source Type: research

Progranulin Reduction Is Associated With Increased Tau Phosphorylation in P301L Tau Transgenic Mice
AbstractGranulin (GRN) mutations have been identified in familial frontotemporal lobar degeneration patients with ubiquitin pathology. GRN transcript haploinsufficiency is proposed as a disease mechanism that leads to the loss of functional progranulin (PGRN) protein. Thus, these mutations are strongly involved in frontotemporal lobar degeneration pathogenesis. Moreover, recent findings indicate that GRN mutations are associated with other neurodegenerative disorders with tau pathology, including Alzheimer disease and corticobasal degeneration. To investigate the potential influence of a decline in PGRN protein on tau accu...
Source: Journal of Neuropathology and Experimental Neurology - January 16, 2015 Category: Neurology Tags: Original Articles Source Type: research

Tau Proteins in the Temporal and Frontal Cortices in Patients With Vascular Dementia
AbstractWe previously reported that, in the brains of older patients with vascular dementia (VaD), there is a distinctive accumulation of detergent-extractable soluble amyloid-β, with a predominance of Aβ42 species. It is unclear, however, if tau proteins also accumulate in the brains of older VaD subjects. Using antibody-specific immunoassays, we assessed concentrations of total tau (t-tau) and phosphorylated tau protein, measured at 3 phosphorylated sites (i.e. Thr181, Ser202/Thr205, and Ser262), as well as synaptophysin in the temporal and frontal cortices of 18 VaD, 16 Alzheimer disease (AD), and 16 normal age-matche...
Source: Journal of Neuropathology and Experimental Neurology - January 16, 2015 Category: Neurology Tags: Original Articles Source Type: research

Adenosine Kinase Expression in Cortical Dysplasia With Balloon Cells: Analysis of Developmental Lineage of Cell Types
AbstractFocal cortical dysplasia type IIB (FCDIIB) is a developmental malformation of the cerebral cortex that is associated with pharmacoresistant epilepsy. Overexpression of adenosine kinase (ADK) has been regarded as a pathologic hallmark of epilepsy. We hypothesized that the epileptogenic mechanisms underlying FCDIIB are related to abnormal ADK expression. We used immunohistochemistry to examine the expression of ADK and of heterogeneous cell population markers of astrocytes (glial fibrillary acidic protein), immature glia (vimentin), immature neurons (neuronal class III beta-tubulin, TUJ1), multipotential progenitor c...
Source: Journal of Neuropathology and Experimental Neurology - January 16, 2015 Category: Neurology Tags: Original Articles Source Type: research

Notch Signaling Activation in Pediatric Low-Grade Astrocytoma
This study suggests a potential role for Notch signaling in pediatric low-grade astrocytoma tumorigenesis and that Notch signaling may be a viable pathway therapeutic target. (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - January 16, 2015 Category: Neurology Tags: Original Articles Source Type: research

High-Resolution Genomic Analysis Does Not Qualify Atypical Plexus Papilloma as a Separate Entity Among Choroid Plexus Tumors
AbstractChoroid plexus tumors are rare neoplasms that mainly affect children. They include papillomas, atypical papillomas, and carcinomas. Detailed genetic studies are rare, and information about their molecular pathogenesis is limited. Molecular inversion probe analysis is a hybridization-based method that represents a reliable tool for the analysis of highly fragmented formalin-fixed paraffin-embedded tissue–derived DNA. Here, analysis of 62 cases showed frequent hyperdiploidy in papillomas and atypical papillomas that appeared very similar in their cytogenetic profiles. In contrast, carcinomas showed mainly losses of...
Source: Journal of Neuropathology and Experimental Neurology - January 16, 2015 Category: Neurology Tags: Original Articles Source Type: research

Cerebral Cortical Aβ42 and PHF-τ in 325 Consecutive Brain Autopsies Stratified by Diagnosis, Location, and APOE
AbstractWe used a novel approach to molecular quantification in standard fixed and embedded tissue to measure amyloid β 42 (Aβ42) and paired helical filament-τ (PHF-τ) in frontal, temporal, and parietal cortices from 325 consecutive brain autopsies collected as part of a population-based study of brain aging and incident dementia in the Seattle area. We observed significant effects of APOE ε4 on Aβ42 levels in both diagnostic groups by disease stage and region. In contrast, we did not observe a significant effect of APOE ε4 on PHF-τ levels by disease stage in any region. Levels of Aβ42 and PHF-τ in cerebral corte...
Source: Journal of Neuropathology and Experimental Neurology - January 16, 2015 Category: Neurology Tags: Original Articles Source Type: research

In This Issue
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - January 16, 2015 Category: Neurology Tags: In This Issue Source Type: research

Tibial Adamantinoma: Late Metastasis to the Brain
No abstract available (Source: Journal of Neuropathology and Experimental Neurology)
Source: Journal of Neuropathology and Experimental Neurology - December 19, 2014 Category: Neurology Tags: Letter to the Editor Source Type: research

Adjuvant Granulocyte Colony-Stimulating Factor Therapy Results in Improved Spatial Learning and Stimulates Hippocampal Neurogenesis in a Mouse Model of Pneumococcal Meningitis
This study investigated the effect of adjuvant G-CSF treatment on cognitive function after pneumococcal meningitis. C57BL/6 mice were infected by subarachnoid injection of Streptococcus pneumoniae serotype 3 and treated with ceftriaxone and G-CSF subcutaneously or ceftriaxone alone for 5 days. Clinical scores, motor performance, and mortality during bacterial meningitis were unaffected by adjuvant G-CSF treatment. No effect of G-CSF treatment on production of proinflammatory cytokines or activation of microglia or astrocytes was observed. The G-CSF treatment did, however, result in hippocampal neurogenesis and improved spa...
Source: Journal of Neuropathology and Experimental Neurology - December 19, 2014 Category: Neurology Tags: Original Articles Source Type: research

Reassessment of Risk Genotypes (GRN, TMEM106B, and ABCC9 Variants) Associated With Hippocampal Sclerosis of Aging Pathology
AbstractHippocampal sclerosis of aging (HS-Aging) is a common high-morbidity neurodegenerative condition in elderly persons. To understand the risk factors for HS-Aging, we analyzed data from the Alzheimer’s Disease Genetics Consortium and correlated the data with clinical and pathologic information from the National Alzheimer’s Coordinating Center database. Overall, 268 research volunteers with HS-Aging and 2,957 controls were included; detailed neuropathologic data were available for all. The study focused on single-nucleotide polymorphisms previously associated with HS-Aging risk: rs5848 (GRN), rs1990622 (TMEM106B),...
Source: Journal of Neuropathology and Experimental Neurology - December 19, 2014 Category: Neurology Tags: Original Articles Source Type: research

Podoplanin: A Marker for Reactive Gliosis in Gliomas and Brain Injury
AbstractReactive astrogliosis is associated with many pathologic processes in the central nervous system, including gliomas. The glycoprotein podoplanin (PDPN) is upregulated in malignant gliomas. Using a syngeneic intracranial glioma mouse model, we show that PDPN is highly expressed in a subset of glial fibrillary acidic protein–positive astrocytes within and adjacent to gliomas. The expression of PDPN in tumor-associated reactive astrocytes was confirmed by its colocalization with the astrocytic marker S100β and with connexin43, a major astrocytic gap junction protein. To determine whether the increase in PDPN is a g...
Source: Journal of Neuropathology and Experimental Neurology - December 19, 2014 Category: Neurology Tags: Original Articles Source Type: research

Activation Status of Human Microglia Is Dependent on Lesion Formation Stage and Remyelination in Multiple Sclerosis
AbstractSimilar to macrophages, microglia adopt diverse activation states and contribute to repair and tissue damage in multiple sclerosis. Using reverse transcription–quantitative polymerase chain reaction and immunohistochemistry, we show that in vitro M1-polarized (proinflammatory) human adult microglia express the distinctive markers CD74, CD40, CD86, and CCR7, whereas M2 (anti-inflammatory) microglia express mannose receptor and the anti-inflammatory cytokine CCL22. The expression of these markers was assessed in clusters of activated microglia in normal-appearing white matter (preactive lesions) and areas of remyel...
Source: Journal of Neuropathology and Experimental Neurology - December 19, 2014 Category: Neurology Tags: Original Articles Source Type: research

Neuroinflammation and Virus Replication in the Spinal Cord of Simian Immunodeficiency Virus–Infected Macaques
In this study, lumbar spinal cords from SIV-infected pigtailed macaques were examined to quantify SIV replication and associated neuroinflammation. In untreated SIV-infected animals, there was a strong correlation between amount of SIV RNA in the spinal cord and expression of the macrophage marker CD68 and the key proinflammatory mediators tumor necrosis factor and CCL2. We also found a significant correlation between SIV-induced alterations in the spinal cord and the degree of distal epidermal nerve fiber loss among untreated animals. Spinal cord changes (including elevated glial fibrillary acidic protein immunostaining a...
Source: Journal of Neuropathology and Experimental Neurology - December 19, 2014 Category: Neurology Tags: Original Articles Source Type: research

Roundabout 4 Regulates Blood–Tumor Barrier Permeability Through the Modulation of ZO-1, Occludin, and Claudin-5 Expression
AbstractThe blood–tumor barrier (BTB) restricts the delivery of chemotherapeutic drug molecules to tumor tissues. We found that the endothelial cell (EC) receptor molecule Roundabout 4 (Robo4) is endogenously expressed in human brain microvascular ECs and that it is upregulated in a BTB model of glioma cocultured ECs. Knockdown of Robo4 in this BTB model increased permeability; short hairpin RNA targeting Robo4 (shRobo4) led to decreased transendothelial electric resistance values, increased BTB permeability, and downregulated expression of the EC tight junction proteins ZO-1, occludin, and claudin-5. Roundabout 4 influe...
Source: Journal of Neuropathology and Experimental Neurology - December 19, 2014 Category: Neurology Tags: Original Articles Source Type: research