Brain Pathology (Brain Pathol )

Publisher: International Society of Neuropathology, Blackwell Publishing

Description

Brain Pathology is the journal of choice for biomedical scientists investigating diseases of the nervous system. The official journal of the International Society of Neuropathology, Brain Pathology is a peer-reviewed quarterly publication that includes original research, review articles and symposia focuses on the pathogenesis of neurological disease.

  • Impact factor
    4.74
  • 5-year impact
    5.05
  • Cited half-life
    5.90
  • Immediacy index
    1.00
  • Eigenfactor
    0.01
  • Article influence
    1.60
  • Website
    Brain Pathology website
  • Other titles
    Brain pathology (Zurich, Switzerland: Online)
  • ISSN
    1750-3639
  • OCLC
    60627054
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Blackwell Publishing

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • Some journals impose embargoes typically of 6 or 12 months, occasionally of 24 months
    • no listing of affected journals available as yet
  • Conditions
    • See Wiley-Blackwell entry for articles after February 2007
    • Publisher version cannot be used
    • On author or institutional or subject-based server
    • Server must be non-commercial
    • Publisher copyright and source must be acknowledged with set statement ("The definitive version is available at www.blackwell-synergy.com ")
    • Articles in some journals can be made Open Access on payment of additional charge
    • 'Blackwell Publishing' is an imprint of 'Wiley-Blackwell'
  • Classification
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterised by the presence of α-synuclein-containing Lewy bodies and Lewy neurites. However, both dementias also show variable degrees of Alzheimer's disease (AD) pathology (senile plaques and neurofibrillary tangles), particularly in areas of the cortex associated with higher cognitive functions. This study investigates the contribution of the individual and combined pathologies in determining the rate of cognitive decline. Cortical α-synuclein, phosphorylated-tau (phosphotau) and Aβ plaque pathology in 34 PDD and 55 DLB patients was assessed semi-quantitatively in four regions of the neocortex. The decline in cognition, assessed by Mini Mental State Examination, correlated positively with the cortical α-synuclein load. Patients also had varying degrees of senile Aβ plaque and phosphotau pathology. Regression analyses pointed to a combined pathology (Aβ plaque plus phosphotau plus α-synuclein positive features), particularly in the prefrontal cortex (BA9) and temporal lobe neocortex with the superior and middle temporal gyrus (BA 21, 22), being a major determining factor in the development of dementia. Thus, cognitive decline in Lewy body dementias is not a consequence of α-synuclein induced neurodegeneration alone but senile plaque and phosphorylated tau pathology also contribute to the overall deficits.
    Brain Pathology 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alaskan Husky encephalopathy (AHE1) is a fatal brain disease associated with a mutation in SLC19A3.1 (c.624insTTGC, c.625C>A). This gene encodes for a thiamine transporter 2 with a predominantely CNS distribution. Considering that brain is particularly vulnerable to thiamine deficiency due to its reliance on TPP-dependent metabolic pathways involved in energy metabolism and neurotransmitter synthesis, we characterized the impact of this mutation on thiamine status, brain bioenergetics, and the contribution of oxidative stress to this phenotype. In silico modeling of the mutated transporter indicated a significant loss of alpha-helices resulting in a more open portein structure suggesting an impaired thiamine transport ability. The cerebral cortex and thalamus of affected dogs were severely deficient in TPP-dependent enzymes accompanied by decreases in mitochondrial mass and OXPHOS capacity, and increases in oxidative stress. These results along with the behavioral and pathological findings indicate that the phenotype associated with AHE is consistent with a brain-specific thiamine deficiency, leading to brain mitochondrial dysfunction and increased oxidative stress. While some of the biochemical deficits, neurobehavior and affected brain areas in AHE were shared by Wernicke's and Korsakoff's syndromes, several differences were noted likely arising from a tissue-specific vs. that from a whole-body thiamine deficiency.
    Brain Pathology 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Subarachnoid hemorrhage secondary to rupture of an intracranial aneurysm is a highly lethal medical condition. Current management strategies for unruptured intracranial aneurysms involve radiological surveillance and neurosurgical or endovascular interventions. There is no pharmacological treatment available to decrease the risk of aneurysm rupture and subsequent subarachnoid haemorrhage. There is growing interest in the pathogenesis of intracranial aneurysm focused on the development of drug therapies to decrease the incidence of aneurysm rupture. The study of rodent models of intracranial aneurysms has the potential to improve our understanding of intracranial aneurysm development and progression. This review summarises current mouse models of intact and ruptured intracranial aneurysms and discusses the relevance of these models to human intracranial aneurysms. The article also reviews the importance of these models in investigating the molecular mechanisms involved in the disease. Finally, potential pharmaceutical targets for intracranial aneurysm suggested by previous studies are discussed. Examples of potential drug targets include matrix metalloproteinases, stromal cell-derived factor-1, tumor necrosis factor-α, the renin-angiotensin system and the β estrogen receptor. An agreed clear, precise and reproducible definition of what constitutes an aneurysm in the models would assist in their use to better understand the pathology of intracranial aneurysm and apply findings to patients.
    Brain Pathology 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The majority of pediatric low grade gliomas (LGGs) are characterized by constitutive activation of the mitogen activated protein kinase (MAPK) pathway through various mechanisms including BRAF mutations, inactivation of NF1, and KIAA1549-BRAF and FAM131B-BRAF fusions. The KIAA1549-BRAF fusion typically results from a 2.0 Mb tandem duplication in chromosome band 7q34. In the present study, single nucleotide polymorphism (SNP)-based array analysis of three LGGs demonstrated deletions in 7q34 that resulted in a BRAF fusion. Case 1 was likely a pilocytic astrocytoma (PA) with three deletions in 7q33q34 and an exon15-9 KIAA1549-BRAF fusion. SNP array analysis of case 2, a possible dysembryoplastic neuroepithelial tumor (DNT), revealed a 2.6 Mb deletion which included the 5` end of BRAF and extended to the 3` end of FAM131B. In case 3, deletions involving BRAF and FAM131B were observed in both a primary and recurrent PA. RNA-based sequence analysis of cases 2 and 3 confirmed a fusion between FAM131B exon 2 and BRAF exon 9. The presence of fusion transcripts in these three LGGs highlights the utility of SNP array analysis to identify deletions that are suggestive of fusion proteins. BRAF fusions can result from multiple non-overlapping deletions suggesting various complex mechanisms of formation.
    Brain Pathology 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sturge-Weber syndrome (SWS) is a rare syndrome characterized by capillary-venous malformations involving skin and brain. Many patients with SWS also suffer from drug resistant epilepsy. We retrospectively studied a series of six SWS patients with epilepsy and extensive neurosurgical resections. At time of surgery, the patients’ age ranged from 11 to 35 years (with a mean of 20.2 years). All surgical specimens were well-preserved which allowed a systematic microscopical inspection utilizing the 2011 ILAE classification for Focal Cortical Dysplasia (FCD). Neuropathology revealed dysmorphic-like neurons with hypertrophic cell bodies reminiscent to those described for FCD Type IIa in all cases. However, gross architectural abnormalities of neocortical layering typical for FCD Type IIa were missing, and we propose to classify this pattern as FCD ILAE Type IIIc. In addition, our patients with earliest seizure onset also showed polymicrogyria (PMG; n=4). The ictal onset zones were identified in all patients by subdural electrodes, and these areas always showed histopathological evidence for FCD Type IIIc. Four out of five patients had favorable seizure control after surgery with a mean follow-up period of 1.7 years. We concluded from our study that FCD Type IIIc and PMG are frequently associated findings in SWS. FCD Type IIIc may play a major epileptogenic role in SWS and complete resection of the associated FCD should be considered a prognostic key factor to achieve seizure control.
    Brain Pathology 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The association between p53 immunohistochemistry and TP53 mutation status has been controversial. The present study aims to re-evaluate the efficacy of p53 immunohistochemistry to predict the mutational status of TP53. A total of 157 diffuse gliomas (World Health Organization grade II to IV) were assessed by exon-by-exon DNA sequencing from exon 4 through 10 of TP53 using frozen tissue samples. Immunohistochemistry with a p53 antibody (DO-7) on paired formalin-fixed paraffin-embedded materials was assessed for the extent and intensity of reactivity in all cases. A total of 72 mutations were detected in 66 samples. They included 60 missense mutations, 5 nonsense mutations, 4 deletions, and 3 alterations in the splicing sites. A Receiver Operating Characteristic curve analysis revealed that strong p53 immunoreactivity in more than 10 % of cells provided the most accurate prediction of mutation. Using this cut-off value, 52 of 55 immunopositive cases harbored a mutation, while only 14 of 102 immunonegative cases showed mutations, sensitivity and specificity being 78.8% and 96.7 %. Tumors with frameshift mutations frequently showed negative immunostaining. Staining interpretation by an independent observer yielded comparable accuracy. We thus propose p53 immunohistochemistry as a moderately sensitive and highly specific marker to predict TP53 mutation.
    Brain Pathology 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD) might develop olfactory dysfunction that correlates with progression of disease. Alteration of olfactory neuroepithelium associated with MCI may be useful as predictor of cognitive decline. Biomarkers with higher sensitivity and specificity would allow to understand the biological progression of the pathology in association with the clinical course of the disease. In this study, MRI images, apolipoprotein E (ApoE) load, Olfactory Connecticut test and Montreal Cognitive Assesment (MoCA) indexes were obtained from non cognitive impaired (NCI), MCI and AD patients. We established culture of patient-derived olfactory stromal cells from biopsies of olfactory mucosa (OM) to test whether biological properties of mesenchymal stromal cells (MSC) are concurrent with MCI and AD psychophysical pathology. We determined expression of amyloid Aβ peptides in the neuroepithelium of tissue sections from MCI and AD, as well as in cultured cells of olfactory mucosa. Reduced migration and proliferation of stromal (CD90+) cells in MCI and AD with respect to NCI patients was determined. A higher proportion of anosmic MCI and AD cases were concurrent with the ApoE ε4 allele. In summary, dysmetabolism of amyloid was concurrent with migration and proliferation impairment of patient-derived stem cells.
    Brain Pathology 07/2014;
  • Brain Pathology 07/2014; 24(4):423-4.
  • Brain Pathology 07/2014; 24(4):417-8.
  • Brain Pathology 07/2014; 24(4):415-6.
  • [Show abstract] [Hide abstract]
    ABSTRACT: While World Health Organization (WHO) grading of meningioma stratifies patients according to recurrence risk overall, there is substantial within-grade heterogeneity with respect to recurrence-free survival (RFS). Most meningiomas are graded according to mitotic counts per unit area on H&E sections, a method potentially confounded by tumor cellularity, as well as potential limitations of accurate mitotic figure detection on routine histology. To refine mitotic figure assessment we evaluated 363 meningiomas with phospho-histoneH3(Ser10), and determined the mitotic index (number of mitoses per 1000 tumor cells). The median mitotic indices among WHO grades I (n=268), II (n=84), and III (n=11) tumors were 1, 4, and 12, Classification and regression tree analysis to categorize cutoffs identified 3 subgroups defined by mitotic indices of 0-2, 3-4, and ≥5, which on univariate analysis were associated with RFS (p<0.01). In multivariate analysis, mitotic index subgrouped in this manner was significantly associated with RFS (p<0.01) after adjustment for Simpson grade, WHO grade, and MIB-1 index. Mitotic index was then examined within individual WHO grade, showing that for grade I and II meningiomas, mitotic index can add additional information to RFS risk. The results suggest that the use of a robust mitotic marker in meningioma could refine risk stratification.
    Brain Pathology 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization (WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, The Netherlands, under the sponsorship of the International Society for Neuropathology (ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present “white paper” catalogues the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided “ISN-Haarlem” guidelines. Salient recommendations include that: 1) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; 2) diagnoses should be “layered” with histologic classification, WHO grade, and molecular information listed below an “integrated diagnosis”; 3) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; 4) some pediatric entities should be separated from their adult counterparts; 5) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology and 6) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the 4th Edition of the WHO classification of central nervous system tumors.
    Brain Pathology 07/2014;
  • Brain Pathology 07/2014; 24(4):421-2.
  • Brain Pathology 07/2014; 24(4):419-20.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Axonal degeneration is one of the initial steps in many neurological disorders and has been associated with increased autophagic activity. Although there is increasing data on the regulation of autophagy proteins in the neuronal soma after spinal cord injury (SCI), their characterization in the axon is scarce. Here, we examined the regulation of autophagy during axonal degeneration in a rat model of SCI following a lesion at Th 8. We analyzed the morphological and ultrastructural changes in injured axons by immunohistochemical evaluation of autophagy-related proteins and electron microscopy at different time points following SCI. The expression of ULK1, Atg7 and Atg5 in damaged axons was rapidly upregulated within hours after SCI. The number of axonal LC3-positive autophagosomes was also rapidly increased after SCI and remained at an increased level for up to six weeks. Ultrastructural analysis showed early signs of axonal degeneration and increased autophagy. In conclusion, we show that autophagy is increased early and for a sustained period in degenerating axons after SCI and that it might be an important executive step involved in axonal degeneration. Therefore, autophagy may represent a promising target for future therapeutic interventions in the treatment of axonal degeneration in traumatic central nervous system disorders.
    Brain Pathology 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tissue fibrosis, or scar formation, is a common response to damage in most organs of the body. The central nervous system (CNS) is special in that fibrogenic cells are restricted to vascular and meningeal niches. However, disruption of the blood-brain barrier and inflammation can unleash stromal cells and trigger scar formation. Astroglia segregate from the inflammatory lesion core, and the so-called "glial scar" composed of hypertrophic astrocytes seals off the intact neural tissue from damage. In the lesion core, a second type of "fibrotic scar" develops, which is sensitive to inflammatory mediators. Genetic fate mapping studies suggest that pericytes and perivascular fibroblasts are activated, but other precursor cells may also be involved in generating a transient fibrous extracellular matrix in the CNS. The stromal cells sense inflammation and attract immune cells, which in turn drive myofibroblast transdifferentiation. We believe that the fibrotic scar represents a major barrier to CNS regeneration. Targeting of fibrosis may therefore prove to be a valuable therapeutic strategy for neurological disorders such as stroke, spinal cord injury and multiple sclerosis.
    Brain Pathology 07/2014; 24(4):404-413.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pericytes are cells in the blood-brain barrier (BBB) that degenerate in Alzheimer's disease (AD), a neurodegenerative disorder characterized by early neurovascular dysfunction, elevation of amyloid β-peptide (Aβ), tau pathology and neuronal loss, leading to progressive cognitive decline and dementia. Pericytes are uniquely positioned within the neurovascular unit between endothelial cells of brain capillaries, astrocytes and neurons. Recent studies have shown that pericytes regulate key neurovascular functions including BBB formation and maintenance, vascular stability and angioarchitecture, regulation of capillary blood flow, and clearance of toxic cellular by-products necessary for normal functioning of the central nervous system (CNS). Here, we review the concept of the neurovascular unit and neurovascular functions of CNS pericytes. Next, we discuss vascular contributions to AD and review new roles of pericytes in the pathogenesis of AD such as vascular-mediated Aβ-independent neurodegeneration, regulation of Aβ clearance and contributions to tau pathology, neuronal loss and cognitive decline. We conclude that future studies should focus on molecular mechanisms and pathways underlying aberrant signal transduction between pericytes and its neighboring cells within the neurovascular unit, that is, endothelial cells, astrocytes and neurons, which could represent potential therapeutic targets to control pericyte degeneration in AD and the resulting secondary vascular and neuronal degeneration.
    Brain Pathology 07/2014; 24(4):371-386.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Subpial cortical demyelination (SCD) accounts for the greatest proportion of demyelinated cortex in multiple sclerosis (MS). SCD is already found in biopsy cases with early MS and in marmosets with experimental autoimmune encephalomyelitis (EAE), but the pathogenesis of SCD is not well understood. The objective of this study was to investigate whether and, if so, which meningeal inflammatory cells were associated with early SCD in marmosets with EAE.Immunohistochemistry was performed to analyze brain samples from 8 control animals and 8 marmosets immunized with myelin oligodendrocyte glycoprotein. Meningeal T, B and plasma cells were quantified adjacent to SCD, normal-appearing EAE cortex (NAC) and control marmoset cortex. SCD areas appeared mostly hypocellular with low-grade microglial activation. In marmosets with EAE, meninges adjacent to SCD showed significantly increased T cells paralleled by elevated plasma cells, but unaltered B cell numbers compared to NAC. The elevation of meningeal T and plasma cells was a specific finding topographically associated with SCD, since the meninges overlying NAC displayed similarly low T, B and plasma cell numbers as control cortex. These findings suggest that local meningeal T and plasma cell infiltration contributes to the pathogenesis of SCD in marmosets with EAE.
    Brain Pathology 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: In 2011 a large outbreak of Shiga toxin producing Enterohaemorrhagic Escherichia coli (EHEC) infections occurred in northern Germany which mainly affected adults. 104 out of 3,842 patients experienced a complicated course comprising haemolytic uremic syndrome and neurological complications including cognitive impairment, aphasia, seizures and coma. T2 hyperintensities on Magnet Resonance Imaging (MRI) bilateral in the thalami and in the dorsal pons were found suggestive for a metabolic toxic effect. Five of the 104 patients died due to toxic heart failure. In the present study the post-mortem neuropathological findings of the five EHEC patients are described. Histological investigation of 13 brain regions (frontal-, temporal-, occipital cortex, corpora mamillaria, thalamus, frontal operculum, corona radiata, gyrus angularis, pons, medulla oblongata, cerebellar vermis and cerebellar hemisphere) showed no thrombosis, ischemic changes, or fresh infarctions. Further, no changes were found in electron microscopy. In comparison with 5 age matched controls slightly increased activation of microglia and a higher neuronal expression of interleukin-1β and of Shiga toxin receptor CD77/ globotriaosylceramide 3 was observed. The findings were confirmed by Western blot analyses. It is suggested that CD77/globotriaosylceramide up-regulation may be a consequence to Shiga toxin-exposure whereas increased interleukin-1β expression may point to activation of inflammatory cascades.
    Brain Pathology 07/2014;

Related Journals