Journal of Neuropathology & Experimental Neurology最新文献_第3页

Quantitative Analysis of the Cellular Microenvironment of Glioblastoma to Develop Predictive Statistical Models of Overall Survival 胶质母细胞瘤细胞微环境的定量分析，以建立总体生存的预测统计模型

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-12-01 DOI: 10.1093/jnen/nlw090

Jessica X. Yuan, F. Bafakih, J. Mandell, B. Horton, J. Munson

{"title":"Quantitative Analysis of the Cellular Microenvironment of Glioblastoma to Develop Predictive Statistical Models of Overall Survival","authors":"Jessica X. Yuan, F. Bafakih, J. Mandell, B. Horton, J. Munson","doi":"10.1093/jnen/nlw090","DOIUrl":"https://doi.org/10.1093/jnen/nlw090","url":null,"abstract":"Glioblastomas, the most common primary malignant brain tumors, have a distinct tissue microenvironment. Although non-neoplastic cells contribute to glioblastoma progression, very few quantitative studies have shown the effect of tumor microenvironmental influences on patient survival. We examined relationships of the cellular microenvironment, including astrocytes, microglia, oligodendrocytes, and blood vessels, to survival in glioblastoma patients. Using histological staining and quantitative image analyses, we examined the tumor-associated parenchyma of 33 patients and developed statistical models to predict patient outcomes based on the cellular picture of the tumor parenchyma. We found that blood vessel density correlated with poorer prognosis. To examine the role of adjacent parenchymal versus higher tumor cell density bulk parenchymal tissue, we examined the glial components in these highly variable regions. Comparison of bulk and adjacent astrocytes and microglia in tissue yielded the strongest prediction of survival, with high levels of adjacent astrocytes predicted poor prognosis and high levels of microglia correlated with a better prognosis. These results indicate that parenchymal components predict survival in glioblastoma patients and in particular that the balance between reactive glial populations is important for patient prognosis.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90638092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Endothelial Cell Hypertrophy and Microvascular Proliferation in Meningiomas Are Correlated with Higher Histological Grade and Shorter Progression-Free Survival 脑膜瘤的内皮细胞肥大和微血管增生与较高的组织学分级和较短的无进展生存期相关

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-12-01 DOI: 10.1093/jnen/nlw095

C. Ling, Celso Pouget, F. Rech, Robin Pflaum, M. Treffel, F. Bielle, K. Mokhtari, Jean-Matthieu Casse, J. Vignaud, M. Kalamarides, M. Peyre, G. Gauchotte

{"title":"Endothelial Cell Hypertrophy and Microvascular Proliferation in Meningiomas Are Correlated with Higher Histological Grade and Shorter Progression-Free Survival","authors":"C. Ling, Celso Pouget, F. Rech, Robin Pflaum, M. Treffel, F. Bielle, K. Mokhtari, Jean-Matthieu Casse, J. Vignaud, M. Kalamarides, M. Peyre, G. Gauchotte","doi":"10.1093/jnen/nlw095","DOIUrl":"https://doi.org/10.1093/jnen/nlw095","url":null,"abstract":"Microvascular proliferation (MVP) is a hallmark of glioblastoma. Endothelial cell hypertrophy (ECH), also known as endothelial hyperplasia, is correlated with a shorter survival of patients with gliomas. However, the prognostic value of these 2 morphological features has not been studied in meningiomas. The aim of this study was to evaluate the prognostic value of angiogenesis in meningiomas, most notably ECH, MVP, and microvascular density, which were evaluated using immunohistochemistry with antibodies against CD34 and CD105 (a marker of neovascularization) in a series of 139 meningiomas. ECH, MVP, and CD105 immunoreactivity were significantly correlated with higher histological grades (p < 0.0001, p = 0.0004, and p = 0.0003, respectively). ECH and MVP but not CD105 immunoreactivities were significantly correlated with a shorter progression-free survival time (PFS) (p = 0.017, p = 0.021, and p = 0.137, respectively). In Cox multivariate analysis, ECH was an independent predictor of shorter PFS (p = 0.028). Therefore, ECH and MVP are markers of shorter PFS in meningiomas and are significantly correlated with grade. These findings give insight into the use of anti-angiogenic therapies. Further studies are needed to determine whether these markers could allow us to identify patients who could benefit from anti-angiogenic therapies.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78033076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Shared and Distinct Patterns of Oligodendroglial Response in &agr;-Synucleinopathies and Tauopathies 少突胶质反应在&agr;-突触核蛋白病和tau病中的共享和独特模式

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-12-01 DOI: 10.1093/jnen/nlw087

Z. Rohan, I. Milenkovic, Mirjam I. Lutz, R. Matěj, G. Kovacs

{"title":"Shared and Distinct Patterns of Oligodendroglial Response in &agr;-Synucleinopathies and Tauopathies","authors":"Z. Rohan, I. Milenkovic, Mirjam I. Lutz, R. Matěj, G. Kovacs","doi":"10.1093/jnen/nlw087","DOIUrl":"https://doi.org/10.1093/jnen/nlw087","url":null,"abstract":"Pathological protein deposits in oligodendroglia are common but variable features of various neurodegenerative conditions. To evaluate oligodendrocyte response in neurodegenerative diseases (NDDs) with different extents of oligodendroglial protein deposition we performed immunostaining for tubulin polymerization-promoting protein p25&agr; (TPPP/p25&agr;), &agr;-synuclein (&agr;-syn), phospho-tau, ubiquitin, myelin basic protein, and the microglial marker HLA-DR. We investigated cases of multiple system atrophy ([MSA] n = 10), Lewy body disease ([LBD] n = 10), globular glial tauopathy ([GGT] n = 7) and progressive supranuclear palsy ([PSP] n = 10). Loss of nuclear TPPP/p25&agr; immunoreactivity correlated significantly with the degree of microglial reaction and loss of myelin basic prtein density as a marker of tract degeneration. This was more prominent in MSA and GGT, which, together with enlarged cytoplasmic TPPP/p25&agr; immunoreactivity and inclusion burden allowed these disorders to be grouped as predominant oligodendroglial proteinopathies. However, distinct features, ie more colocalization of &agr;-syn than tau with TPPP/p25&agr;, more obvious loss of oligodendrocyte density in MSA, but more prominent association of tau protein inclusions in GGT to loss of nuclear TPPP/p25&agr; immunoreactivity, were also recognized. In addition, we observed previously underappreciated oligodendroglial &agr;-synuclein pathology in the pallidothalamic tract in LBD. Our study demonstrates common and distinct aspects of oligodendroglial involvement in the pathogenesis of diverse NDDs.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84238448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 32

Histopathologic Analysis of Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL): A Report of a New Genetically Confirmed Case and Comparison to 2 Previous Cases 脑常染色体隐性动脉病伴皮层下梗死和脑白质病(CARASIL)的组织病理学分析:1例新遗传确诊病例并与既往2例病例比较

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-11-01 DOI: 10.1093/jnen/nlw078

S. Ito, M. Takao, T. Fukutake, H. Hatsuta, Sayaka Funabe, N. Ito, Y. Shimoe, T. Niki, I. Nakano, M. Fukayama, S. Murayama

{"title":"Histopathologic Analysis of Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL): A Report of a New Genetically Confirmed Case and Comparison to 2 Previous Cases","authors":"S. Ito, M. Takao, T. Fukutake, H. Hatsuta, Sayaka Funabe, N. Ito, Y. Shimoe, T. Niki, I. Nakano, M. Fukayama, S. Murayama","doi":"10.1093/jnen/nlw078","DOIUrl":"https://doi.org/10.1093/jnen/nlw078","url":null,"abstract":"Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a nonhypertensive hereditary cerebral small vessel disease that is caused by mutations in a single gene, HTRA1. The HTRA1 protein normally represses transforming growth factor-&bgr; (TGF-&bgr;) signaling and its mutations result in vascular changes. Ten homozygous, 1 compound heterozygous, and 1 homozygous frameshift mutation have been identified in the HTRA1 gene of patients with genetically confirmed CARASIL. However, few studies have compared neuropathologic findings in patients with the same or different mutations in HTRA1. We analyzed histopathologic alterations in 3 autopsied patients with genetically confirmed CARASIL: 2 of them had the HTRA1 p.R302X mutation and 1 had the HTRA1 p.A252T mutation. All 3 had similar cerebral arteriopathy showing myointimal proliferation, multi-layering and splitting of elastic laminae, and marked loss of medial smooth muscle cells. One CARASIL patient with the p.R302X mutation had atherosclerosis-like intimal thickening and arteriolosclerosis in the arteries of visceral organs, indicating that atherosclerotic changes are not confined to the intracranial vasculature but can occur throughout the body. CARASIL is a unique hereditary disease that shows similar neuropathology, systemic vascular pathology, and other TGF-&bgr;1-related pathology associated with HTRA1 mutation.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86420882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

T-Cells Underlie Some but Not All of the Cerebellar Pathology in a Neonatal Rat Model of Congenital Lymphocytic Choriomeningitis Virus Infection 在先天性淋巴细胞性脉络丛脑膜炎病毒感染的新生大鼠模型中，t细胞是部分但不是全部小脑病理的基础

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-11-01 DOI: 10.1093/jnen/nlw079

H. Klein, Glenda K. Rabe, B. Karacay, D. Bonthius

{"title":"T-Cells Underlie Some but Not All of the Cerebellar Pathology in a Neonatal Rat Model of Congenital Lymphocytic Choriomeningitis Virus Infection","authors":"H. Klein, Glenda K. Rabe, B. Karacay, D. Bonthius","doi":"10.1093/jnen/nlw079","DOIUrl":"https://doi.org/10.1093/jnen/nlw079","url":null,"abstract":"Lymphocytic choriomeningitis virus (LCMV) infection during pregnancy injures the human fetal brain. Neonatal rats inoculated with LCMV are an excellent model of congenital LCMV infection because they develop cerebellar injuries similar to those in humans. To evaluate the role of T-lymphocytes in LCMV-induced cerebellar pathology, congenitally athymic rats, deficient in T-lymphocytes were compared with euthymic rats. Peak viral titers and cellular targets of infection were similar, but viral clearance from astrocytes was impaired in the athymic rats. Cytokines and chemokines rose to higher levels and for a greater duration in the euthymic rats than in their athymic counterparts. The euthymic rats developed an intense lymphocytic infiltration, accompanied by destructive lesions of the cerebellum and a neuronal migration defect because of T-cell-mediated alteration of Bergmann glia. These pathologic changes were absent in the athymic rats but were restored by adoptive transfer of lymphocytes. Athymic rats were not free of pathologic effects, however, as the virus induced cerebellar hypoplasia. Thus, T-lymphocytes play key roles in LCMV clearance, cytokine/chemokine responses, and pathogenesis of destructive lesions and neuronal migration disturbances but not all pathology is T-lymphocyte-dependent. Cerebellar hypoplasia from LCMV occurs even in the absence of T-lymphocytes and is likely due to the viral infection itself.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87349617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Radiation-Induced Cerebral Vascular “Malformations” at Biopsy 活体组织检查放射诱导的脑血管“畸形”

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-11-01 DOI: 10.1093/jnen/nlw085

B. Kleinschmidt-DeMasters, K. Lillehei

{"title":"Radiation-Induced Cerebral Vascular “Malformations” at Biopsy","authors":"B. Kleinschmidt-DeMasters, K. Lillehei","doi":"10.1093/jnen/nlw085","DOIUrl":"https://doi.org/10.1093/jnen/nlw085","url":null,"abstract":"Radiation-induced vascular “malformations”, designated cavernous hemangiomas/cavernomas (“RICHs”), are seldom biopsied and are usually diagnosed based on neuroimaging features. They are an increasingly recognized complication of both CNS external beam radiation therapy and stereotactic radiosurgery. We identified 13 patients with radiation-induced vascular “malformations” in our surgical neuropathology databases searched from 2000 to 2016; 4 had received their therapy during childhood; 5 had received radiosurgery. Inclusion required identifiable vascular abnormalities on neuroimaging and/or, if recurrent tumor was additionally present, the vascular lesion had been a separately submitted specimen at the time of resection. Trichrome, and elastic stains and immunohistochemistry (IHC) for CD31, CD34, and smooth muscle actin (SMA) were performed. Five RICHs showed histological and IHC overlap with 12 non-radiation-induced cavernomas; 8/13 had organizing coagulum containing recanalized vasculature and fibrinous deposits. Markedly altered vasculature in these 8 lacked the back-to-back caverns typical of cavernomas; there was near absence of SMA immunopositivity in their ill-defined vessel walls. These coagulum-like lesions likely represented organized fibrinous exudates caused by subacute/remote radiation-induced fibrinoid vascular necrosis and vascular leakage. Thus, RICHs occur as 2 distinct histological types, without direct correlation between histological type and age at receipt, or type, of radiation. Two different etiological mechanisms likely underlie their pathogenesis.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77765433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

C-Terminal-Deleted Prion Protein Fragment Is a Major Accumulated Component of Systemic PrP Deposits in Hereditary Prion Disease With a 2-Bp (CT) Deletion in PRNP Codon 178 在PRNP密码子178中有2 bp (CT)缺失，c端缺失的朊蛋白片段是遗传性朊病毒疾病中系统性PrP沉积的主要累积成分

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-11-01 DOI: 10.1093/jnen/nlw077

H. Honda, K. Matsuzono, S. Fushimi, Kota Sato, Satoshi O. Suzuki, K. Abe, T. Iwaki

{"title":"C-Terminal-Deleted Prion Protein Fragment Is a Major Accumulated Component of Systemic PrP Deposits in Hereditary Prion Disease With a 2-Bp (CT) Deletion in PRNP Codon 178","authors":"H. Honda, K. Matsuzono, S. Fushimi, Kota Sato, Satoshi O. Suzuki, K. Abe, T. Iwaki","doi":"10.1093/jnen/nlw077","DOIUrl":"https://doi.org/10.1093/jnen/nlw077","url":null,"abstract":"Prion protein (PrP) has 2 glycosylated sites and a glycosylphosphatidylinositol (GPI) anchor on the C-terminal. Reports on genetic prion disease with GPI anchorless PrP are very limited. In this study, we characterized the molecular alterations of mutated PrP in a 37-year-old female autopsy case with a recently identified PRNP mutation involving a 2-bp deletion in codon 178 that results in a premature stop codon mutation in codon 203. Postmortem examination revealed numerous irregularly shaped coarse PrP deposits and multicentric plaques in the brain that were mainly comprised of C-terminal deleted abnormal PrP primarily derived from the mutant allele. Additionally, abnormal PrP deposits were detected in almost all other examined organs. PrP was mainly deposited in peripheral nerves, smooth muscles, and blood vessels in non-CNS tissues. Western blot analysis after proteinase K treatment showed protease-resistant PrP (PrPres) signals with a molecular weight of 9 kDa; weak PrPres smear signals of 9 to ∼80 kDa were also noted. Gel filtration revealed that PrPres oligomers were mainly composed of the PrP fragments. In conclusion, the mutated PrP lacking that GPI anchor was truncated shortly and deposited in almost every examined organ.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78561196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Pediatric Neuropathology in Africa: Local Experience in Nigeria and Challenges and Prospects for the Continent 非洲的小儿神经病理学:尼日利亚的地方经验以及非洲大陆的挑战和前景

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-09-15 DOI: 10.1093/jnen/nlw076

B. Olasode, Chiazor Udochukwu Onyia

{"title":"Pediatric Neuropathology in Africa: Local Experience in Nigeria and Challenges and Prospects for the Continent","authors":"B. Olasode, Chiazor Udochukwu Onyia","doi":"10.1093/jnen/nlw076","DOIUrl":"https://doi.org/10.1093/jnen/nlw076","url":null,"abstract":"The present state of pediatric neuropathology practice is in rudimentary developmental stages in most parts of sub-Saharan Africa. We sought to determine the pattern of neurosurgical lesions in children diagnosed in southwestern Nigeria and briefly address issues surrounding the practice of this aspect of pathology in Africa. We performed a retrospective review of histopathologic results of biopsies obtained from pediatric patients with neurosurgical lesions at the Department of Pathology, Obafemi Awolowo University Teaching Hospitals Complex, Ile–Ife, Nigeria, between January 2001 and December 2011. Demographic and clinical data were extracted from the Ife-Ijesha cancer registry and histopathological diagnoses were confirmed. A total of 111 biopsies were reviewed with a maximum of 17 in 2001 and minimum of 3 in 2005. Patient ages ranged between 1 day and 16 years with a male:female ratio of 1.02:1. There were 53 spinal lesions, 15 intracranial lesions, 36 scalp masses, 6 skull lesions and 1 muscle biopsy. Most of the specimens were from myelomeningoceles. This documentation of the major types of pediatric neurological conditions encountered in clinical practice in this relatively resource-limited setting indicate the need for collaboration with better developed centers to improve training in neurosurgery and neuropathology to enhance the quality of clinical care for young patients in Africa.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84958684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

American Association of Neuropathologists, Inc. Abstracts of the 92nd Annual Meeting June 16–19, 2016 Baltimore, MD 美国神经病理学家协会第92届年会摘要2016年6月16-19日，马里兰州巴尔的摩

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-06-01 DOI: 10.1093/jnen/nlw038

F. Rodriguez, D. Hill, Cheng-Ying Ho, A. Melo, F. Tovar-Moll, P. Oliveira-Szejnfeld, A. Camacho, G. C. Gomes, F. O. Melo, A. G. M. Batista, H. N. Machado, E. Awad, Thales A. Ferreira, R. Andrade, R. Mello, M. Arruda, R. Brindeiro, Rodrigo Delvechio, A. Tanuri

{"title":"American Association of Neuropathologists, Inc. Abstracts of the 92nd Annual Meeting June 16–19, 2016 Baltimore, MD","authors":"F. Rodriguez, D. Hill, Cheng-Ying Ho, A. Melo, F. Tovar-Moll, P. Oliveira-Szejnfeld, A. Camacho, G. C. Gomes, F. O. Melo, A. G. M. Batista, H. N. Machado, E. Awad, Thales A. Ferreira, R. Andrade, R. Mello, M. Arruda, R. Brindeiro, Rodrigo Delvechio, A. Tanuri","doi":"10.1093/jnen/nlw038","DOIUrl":"https://doi.org/10.1093/jnen/nlw038","url":null,"abstract":"Congenital Zika virus infection is a developing public health emergency, leading to microcephaly, intracerebral calcifications, and often fetal death. Here we present the neuropathological findings from an autopsy of a 20week fetus in which congenital Zika virus infection was diagnosed in utero. Though microcephaly or intracerebral calcification was not yet identified, fetal ultrasound and MRI findings revealed mild hydrocephalus with a markedly thinned cortical rim and partial corpus callosum agenesis. Following pregnancy termination, autopsy revealed a brain within the normal weight range for gestational age, however the thinned cortex was grossly notable. Histologic evaluation of the brain showed abundant apoptosis diffusely involving the “intermediately differentiated” neurons in neocortex. The subventricular zone and white matter demonstrated severe volume loss with axonal injuries and macrophage infiltrates. Additionally, an aggregate of intracellular particles identified on electron microscopy was consistent with viral infection. There was relative sparing of the developmentally mature deep grey matter nuclei and limbic regions, which showed only rare microglial aggregates. Similarly, the germinal matrix of the ganglionic eminence was morphologically intact and void of inflammation. Our imaging and pathologic findings suggest that the Zika virus-associated brain injury is likely a consequence of direct viral injury and post-infectious inflammatory damage to a subpopulation of central nervous sytemsystem cells. Whether the viral infection has an effect on the developmental sequence remains unclear. Future studies across multiple time points of pregnancy will offer better insight into the role of Zika virus infection in brain development.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77446776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Experimental Induction of Cerebral Aneurysms by Developmental Low Copper Diet 发育性低铜饮食诱导脑动脉瘤的实验研究

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-05-01 DOI: 10.1093/jnen/nlw020

Keun-Hwa Jung, K. Chu, Soon-Tae Lee, Y. Shin, Keon-Joo Lee, Dongeon Park, Jung-Suk Yoo, Soyun Kim, Manho Kim, Sang Kun Lee, J. Roh

{"title":"Experimental Induction of Cerebral Aneurysms by Developmental Low Copper Diet","authors":"Keun-Hwa Jung, K. Chu, Soon-Tae Lee, Y. Shin, Keon-Joo Lee, Dongeon Park, Jung-Suk Yoo, Soyun Kim, Manho Kim, Sang Kun Lee, J. Roh","doi":"10.1093/jnen/nlw020","DOIUrl":"https://doi.org/10.1093/jnen/nlw020","url":null,"abstract":"Optimal models are needed to understand the pathophysiology of human cerebral aneurysms (CA). We investigated the development of experimental CA by decreasing the activity of lysyl oxidases by dietary copper deficiency from the time of gestation and then augmenting vascular stress by angiotensin II infusion in adulthood. Rats were fed copper-free, low-copper, or normal diets at different time periods from gestation to adulthood. The incidences of CAs were evaluated and autopsies performed to determine the coexistence of cardiovascular diseases. A copper-free diet from gestation was associated with high mortality rates (79.1%) resulting from rupture of ascending aorta aneurysms; a low-copper diet led to acceptable mortality rates (13.6%) and produced CAs and subarachnoid hemorrhage in 46.4% and 3.6% of animals, respectively. Higher proportions of CAs (up to 33.3%) in the rats primed for copper deficiency from gestation ruptured following angiotensin II infusion from adulthood. Gene expression array analyses of the CAs indicated that genes involving extracellular matrix and vascular remodeling were altered in this model. This model enables future research to understand the entire pathogenetic basis of CA development and rupture in association with systemic vasculopathies.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82629995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12