Journal of Neuropathology & Experimental Neurology最新文献_第6页

A Compact Blast-Induced Traumatic Brain Injury Model in Mice 小型爆炸致小鼠创伤性脑损伤模型的建立

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-02-01 DOI: 10.1093/jnen/nlv019

Hongxing Wang, Y. P. Zhang, Jun Cai, L. Shields, Chad Tuchek, R. Shi, Jianan Li, C. B. Shields, Xiao-Ming Xu

{"title":"A Compact Blast-Induced Traumatic Brain Injury Model in Mice","authors":"Hongxing Wang, Y. P. Zhang, Jun Cai, L. Shields, Chad Tuchek, R. Shi, Jianan Li, C. B. Shields, Xiao-Ming Xu","doi":"10.1093/jnen/nlv019","DOIUrl":"https://doi.org/10.1093/jnen/nlv019","url":null,"abstract":"Blast-induced traumatic brain injury (bTBI) is a common injury on the battlefield and often results in permanent cognitive and neurological abnormalities. We report a novel compact device that creates graded bTBI in mice. The injury severity can be controlled by precise pressures that mimic Friedlander shockwave curves. The mouse head was stabilized with a head fixator, and the body was protected with a metal shield; shockwave durations were 3 to 4 milliseconds. Reflective shockwave peak readings at the position of the mouse head were 12 ± 2.6 psi, 50 ± 20.3 psi, and 100 ± 33.1 psi at 100, 200, and 250 psi predetermined driver chamber pressures, respectively. The bTBIs of 250 psi caused 80% mortality, which decreased to 27% with the metal shield. Brain and lung damage depended on the shockwave duration and amplitude. Cognitive deficits were assessed using the Morris water maze, Y-maze, and open-field tests. Pathological changes in the brain included disruption of the blood-brain barrier, multifocal neuronal and axonal degeneration, and reactive gliosis assessed by Evans Blue dye extravasation, silver and Fluoro-Jade B staining, and glial fibrillary acidic protein immunohistochemistry, respectively. Behavioral and pathological changes were injury severity-dependent. This mouse bTBI model may be useful for investigating injury mechanisms and therapeutic strategies associated with bTBI.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":"44 1","pages":"183–196"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75919078","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: 21

MicroRNA Expression Patterns in Human Astrocytes in Relation to Anatomical Location and Age 人类星形胶质细胞中MicroRNA表达模式与解剖位置和年龄的关系

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-02-01 DOI: 10.1093/jnen/nlv016

V. Rao, S. Ludwin, Shi-Chie Fuh, R. Sawaya, C. Moore, Ming-kai Ho, B. Bedell, H. Sarnat, A. Bar-Or, J. Antel

{"title":"MicroRNA Expression Patterns in Human Astrocytes in Relation to Anatomical Location and Age","authors":"V. Rao, S. Ludwin, Shi-Chie Fuh, R. Sawaya, C. Moore, Ming-kai Ho, B. Bedell, H. Sarnat, A. Bar-Or, J. Antel","doi":"10.1093/jnen/nlv016","DOIUrl":"https://doi.org/10.1093/jnen/nlv016","url":null,"abstract":"Anatomic distribution and age are variables linked to functions of astrocytes under physiologic and pathologic conditions. We measured the relative expression of a panel of microRNAs (miRNAs) in astrocytes captured by laser micro-dissection from normal human adult white and grey matter, human fetal white matter and germinal matrix samples. Although expression of most miRNAs was comparable between adult and fetal samples, regional differences were observed. In the adult cerebral cortex, expression of miRNAs in morphologically distinct inter-laminar astrocytes underlying the glial limitans differed from those in deeper cortical layers, suggesting functional specialization possibly related to structural stability and defense from potentially harmful factors in the cerebrospinal fluid. Differences between adult white and grey matter miRNA expression included higher expression of pro-inflammatory miRNAs in the former, potentially contributing to differences in inflammation between grey and white matter plaques in multiple sclerosis. Lower expression of miRNAs in fetal versus adult white matter astrocytes likely reflects the immaturity of these migrating cells. Highly expressed miRNAs in the fetal germinal matrix are probably relevant in development and also recapitulate some responses to injury. Future studies can address regional alterations of miRNA expression in pathological conditions.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":"30 1","pages":"156–166"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86876765","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: 35

Prognostic and Therapeutic Markers in Chordomas: A Study of 287 Tumors 脊索瘤的预后和治疗指标:287例肿瘤的研究

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-02-01 DOI: 10.1093/jnen/nlv010

A. Tauziède-Espariat, D. Bresson, M. Polivka, Schahrazed Bouazza, F. Labrousse, E. Aronica, J. Prétet, F. Projetti, P. Herman, H. Salle, F. Monnien, S. Valmary-Degano, A. Laquérriere, M. Pocard, L. Chaigneau, N. Isambert, M. Aubriot‐Lorton, L. Feuvret, B. George, S. Froelich, H. Adle-Biassette

{"title":"Prognostic and Therapeutic Markers in Chordomas: A Study of 287 Tumors","authors":"A. Tauziède-Espariat, D. Bresson, M. Polivka, Schahrazed Bouazza, F. Labrousse, E. Aronica, J. Prétet, F. Projetti, P. Herman, H. Salle, F. Monnien, S. Valmary-Degano, A. Laquérriere, M. Pocard, L. Chaigneau, N. Isambert, M. Aubriot‐Lorton, L. Feuvret, B. George, S. Froelich, H. Adle-Biassette","doi":"10.1093/jnen/nlv010","DOIUrl":"https://doi.org/10.1093/jnen/nlv010","url":null,"abstract":"Chordomas are slow-growing malignant neoplasms. Determination of histopathologic prognostic factors using a large cohort study has been limited by their low incidence. In this retrospective study, we investigated the clinical, histopathologic, and immunohistochemical prognostic factors in 287 chordomas from 111 patients assessed by central pathologic review. Expression patterns of a variety of markers, including vascular endothelial growth factor (VEGF), mTOR pathway, c-kit, HER2, epidermal growth factor receptor (EGFR) and STAT3, and KRAS, BRAF, EGFR, and PIK3CA mutations were analyzed. On univariate analysis, the results confirm surgery as the best treatment, as judged by patient progression-free survival (PFS) and overall survival (OS). Proton therapy, the presence of a dedifferentiated component, mitotic figures, and Ki67 and p53 labeling indices correlated with PFS. Necrosis and apoptosis correlated with OS. Based on these findings, we propose a histopathologic grading system that correlates with PFS and OS. On multivariate analysis, extent of resection, tumor grade, and proton therapy were independent prognostic factors of PFS; extent of resection, tumor location, and grade were independent prognostic factors of OS. Based on the expression of EGFR, pSTAT3, VEGF, and mTOR pathway proteins, (in 85.9%, 79.1%, 85.7%, and 46% of chordomas, respectively), and 2 new mutations in the PIK3CA gene, we also provide evidence for potential therapeutic targets.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":"36 1","pages":"111–120"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91061765","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: 58

Altered Levels of Visinin-Like Protein 1 Correspond to Regional Neuronal Loss in Alzheimer Disease and Frontotemporal Lobar Degeneration 阿尔茨海默病和额颞叶变性中视蛋白样蛋白1水平的改变与局部神经元丢失相关

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-02-01 DOI: 10.1093/jnen/nlv018

C. M. Kirkwood, M. MacDonald, Tadhg Schempf, A. V. Vatsavayi, M. Ikonomovic, J. Koppel, Ying Ding, Mai Sun, J. Kofler, O. Lopez, N. Yates, R. Sweet

引用次数: 17

Progenitor/Stem Cell Markers in Brain Adjacent to Glioblastoma: GD3 Ganglioside and NG2 Proteoglycan Expression 脑胶质母细胞瘤附近的祖细胞/干细胞标志物:GD3神经节苷脂和NG2蛋白聚糖的表达

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-02-01 DOI: 10.1093/jnen/nlv012

G. Lama, A. Mangiola, G. Proietti, A. Colabianchi, C. Angelucci, A. D'Alessio, P. De Bonis, M. Geloso, L. Lauriola, Elena Binda, F. Biamonte, M. G. Giuffrida, A. Vescovi, G. Sica

{"title":"Progenitor/Stem Cell Markers in Brain Adjacent to Glioblastoma: GD3 Ganglioside and NG2 Proteoglycan Expression","authors":"G. Lama, A. Mangiola, G. Proietti, A. Colabianchi, C. Angelucci, A. D'Alessio, P. De Bonis, M. Geloso, L. Lauriola, Elena Binda, F. Biamonte, M. G. Giuffrida, A. Vescovi, G. Sica","doi":"10.1093/jnen/nlv012","DOIUrl":"https://doi.org/10.1093/jnen/nlv012","url":null,"abstract":"Characterization of tissue surrounding glioblastoma (GBM) is a focus for translational research because tumor recurrence invariably occurs in this area. We investigated the expression of the progenitor/stem cell markers GD3 ganglioside and NG2 proteoglycan in GBM, peritumor tissue (brain adjacent to tumor, BAT) and cancer stem-like cells (CSCs) isolated from GBM (GCSCs) and BAT (PCSCs). GD3 and NG2 immunohistochemistry was performed in paired GBM and BAT specimens from 40 patients. Double-immunofluorescence was carried out to characterize NG2-positive cells of vessel walls. GD3 and NG2 expression was investigated in GCSCs and PCSCs whose tumorigenicity was also evaluated in Scid/bg mice. GD3 and NG2 expression was higher in tumor tissue than in BAT. NG2 decreased as the distance from tumor margin increased, regardless of the tumor cell presence, whereas GD3 correlated with neoplastic infiltration. In BAT, NG2 was coexpressed with &agr;-smooth muscle actin (&agr;-SMA) in pericytes and with nestin in the endothelium. Higher levels of NG2 mRNA and protein were found in GCSCs while GD3 synthase was expressed at similar levels in the 2 CSC populations. PCSCs had lower tumorigenicity than GCSCs. These data suggest the possible involvement of GD3 and NG2 in pre/pro-tumorigenic events occurring in the complex microenvironment of the tissue surrounding GBM.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":"14 1","pages":"134–147"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88358047","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: 31

Atypical Teratoid/Rhabdoid Tumor (AT/RT) Arising From Ependymoma: A Type of AT/RT Secondarily Developing From Other Primary Central Nervous System Tumors 室管膜瘤引起的非典型畸胎瘤/横纹肌样瘤:一种继发于其他原发性中枢神经系统肿瘤的AT/RT

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-02-01 DOI: 10.1093/jnen/nlv017

S. Nobusawa, J. Hirato, T. Sugai, Naoki Okura, Tatsuya Yamazaki, S. Yamada, H. Ikota, Y. Nakazato, H. Yokoo

{"title":"Atypical Teratoid/Rhabdoid Tumor (AT/RT) Arising From Ependymoma: A Type of AT/RT Secondarily Developing From Other Primary Central Nervous System Tumors","authors":"S. Nobusawa, J. Hirato, T. Sugai, Naoki Okura, Tatsuya Yamazaki, S. Yamada, H. Ikota, Y. Nakazato, H. Yokoo","doi":"10.1093/jnen/nlv017","DOIUrl":"https://doi.org/10.1093/jnen/nlv017","url":null,"abstract":"Atypical teratoid/rhabdoid tumors (AT/RT) are rare, aggressive, embryonal brain tumors that occur most frequently in very young children; they are characterized by rhabdoid cells and loss of INI1 protein nuclear expression. Here, we report the case of a 24-year-old man with a left frontal lobe tumor that was composed mainly of rhabdoid cells showing loss of INI1 nuclear reactivity and polyphenotypic immunohistochemical expression, with a small INI1-positive component of ependymoma. Array comparative genomic hybridization separately conducted for each histologically distinct component revealed 22 shared identical copy number alterations, including loss of heterozygosity of chromosome 22q containing the INI1 locus. Furthermore, we found the C11orf95-RELA fusion gene, the genetic hallmark of supratentorial ependymomas, not only in the ependymoma component but also in the AT/RT component by fluorescence in situ hybridization analysis, suggesting that the AT/RT cells secondarily progressed from the preexisting ependymoma cells. A second genetic inactivating event in the INI1 gene was not detected in the AT/RT component. There are several reported cases of AT/RT (or INI1-negative rhabdoid tumors) arising in the setting of other primary brain tumors (gangliogliomas, pleomorphic xanthoastrocytomas, and high-grade gliomas), but the present case is the first reported AT/RT apparently evolving from an ependymoma.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":"24 1","pages":"167–174"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82827223","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: 29

Cylindrical Spirals in Skeletal Muscles Originate From the Longitudinal Sarcoplasmic Reticulum 骨骼肌的圆柱形螺旋起源于纵肌浆网

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-02-01 DOI: 10.1093/jnen/nlv013

Jingwen Xu, Fu‐Chen Liu, Wei Li, Yuying Zhao, Dandan Zhao, Yue-Bei Luo, Jian-Qiang Lu, Chuan-zhu Yan

{"title":"Cylindrical Spirals in Skeletal Muscles Originate From the Longitudinal Sarcoplasmic Reticulum","authors":"Jingwen Xu, Fu‐Chen Liu, Wei Li, Yuying Zhao, Dandan Zhao, Yue-Bei Luo, Jian-Qiang Lu, Chuan-zhu Yan","doi":"10.1093/jnen/nlv013","DOIUrl":"https://doi.org/10.1093/jnen/nlv013","url":null,"abstract":"Cylindrical spirals (CSs) are rare but distinct subsarcolemmal accumulations in skeletal muscle fibers. To date, CSs have been reported in only 16 patients with a variety of neuromuscular conditions. The origin and composition of CSs are unknown, although there are some morphologic similarities between CSs and tubular aggregates (TAs). To clarify the nature of CSs, we characterized the sarcoplasmic reticulum (SR) and other intracellular membrane system proteins in CSs of muscle biopsies from 2 adult Chinese siblings. Immunohistochemical studies revealed subsarcolemmal immunoreactivity for sarco/endoplasmic reticulum Ca2+-ATPase 1 (SERCA 1) in the longitudinal SR, but no immunoreactivity for calsequestrin in the terminal cisternae or type 1 ryanodine receptor (RYR1) in the junctional SR. Muscles biopsied from 2 patients with TAs showed immunoreactivity not only for SERCA1 but also for other SR proteins, including calsequestrin and RYR1. CSs exhibited no immunoreactivity for the Golgi apparatus marker GM130, the nuclear membrane emerin, desmin, the autophagosome marker LC3, the lysosomal membrane marker LAMP2, dystrophin, or myosin. Our results suggest CSs may originate only from the longitudinal SR, whereas TAs are composed of both the junctional and longitudinal SR. Immunochemical staining with antibodies against calsequestrin and RYR1 help to distinguish these 2 pathological alterations.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":"7 1","pages":"148–155"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85244104","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: 5

Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat 二甲胺四环素可短暂降低新生大鼠重复性创伤性脑损伤后的小胶质细胞/巨噬细胞激活，但会加重认知缺陷

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-01-29 DOI: 10.1093/jnen/nlv021

Lauren A. Hanlon, J. Huh, R. Raghupathi

{"title":"Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat","authors":"Lauren A. Hanlon, J. Huh, R. Raghupathi","doi":"10.1093/jnen/nlv021","DOIUrl":"https://doi.org/10.1093/jnen/nlv021","url":null,"abstract":"Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":"36 1","pages":"214–226"},"PeriodicalIF":0.0,"publicationDate":"2016-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81157027","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: 55

Diffusion Tensor Imaging for Assessing Brain Gray and White Matter Abnormalities in a Feline Model of &agr;-Mannosidosis 扩散张量成像评估猫甘露甘露病模型脑灰质和白质异常

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-01-01 DOI: 10.1093/jnen/nlv007

M. Kumar, J. Duda, Sea Young Yoon, J. Bagel, P. O'donnell, C. Vite, S. Pickup, J. Gee, J. Wolfe, Harish Poptani

{"title":"Diffusion Tensor Imaging for Assessing Brain Gray and White Matter Abnormalities in a Feline Model of &agr;-Mannosidosis","authors":"M. Kumar, J. Duda, Sea Young Yoon, J. Bagel, P. O'donnell, C. Vite, S. Pickup, J. Gee, J. Wolfe, Harish Poptani","doi":"10.1093/jnen/nlv007","DOIUrl":"https://doi.org/10.1093/jnen/nlv007","url":null,"abstract":"&agr;-Mannosidosis (AMD) is an autosomal recessively inherited lysosomal storage disorder affecting brain function and structure. We performed ex vivo and in vivo diffusion tensor imaging (DTI) on the brains of AMD-affected cats to assess gray and white matter abnormalities. A multi-atlas approach was used to generate a brain template to process the ex vivo DTI data. The probabilistic label method was used to measure fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity values from gray and white matter regions from ex vivo DTI. Regional analysis from various regions of the gray matter (frontal cortex, cingulate gyrus, caudate nucleus, hippocampus, thalamus, and occipital cortex), and white matter (corpus callosum, corticospinal tract, cerebral peduncle, external and internal capsule) was also performed on both ex vivo and in vivo DTI. Ex vivo DTI revealed significantly reduced FA from both gray and white matter regions in AMD-affected cats compared to controls. Significantly reduced FA was also observed from in vivo DTI of AMD-affected cats compared to controls, with lower FA values observed in all white matter regions. We also observed significantly increased axial and radial diffusivity values in various gray and white matter regions in AMD cats from both ex vivo and in vivo DTI data. Imaging findings were correlated with histopathologic analyses suggesting that DTI studies can further aid in the characterization of AMD by assessing the microstructural abnormalities in both white and gray matter.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":"1 1","pages":"35–43"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83329407","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: 13

Elevated Expression of the Cerebrospinal Fluid Disease Markers Chromogranin A and Clusterin in Astrocytes of Multiple Sclerosis White Matter Lesions 多发性硬化症白质病变星形胶质细胞中脑脊液疾病标志物嗜铬粒蛋白A和聚簇蛋白的表达升高

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-01-01 DOI: 10.1093/jnen/nlv004

Marvin M. van Luijn, M. van Meurs, M. Stoop, E. Verbraak, A. Wierenga-wolf, M. Melief, K. Kreft, R. Verdijk, B. '. ’t Hart, T. Luider, J. Laman, R. Hintzen

{"title":"Elevated Expression of the Cerebrospinal Fluid Disease Markers Chromogranin A and Clusterin in Astrocytes of Multiple Sclerosis White Matter Lesions","authors":"Marvin M. van Luijn, M. van Meurs, M. Stoop, E. Verbraak, A. Wierenga-wolf, M. Melief, K. Kreft, R. Verdijk, B. '. ’t Hart, T. Luider, J. Laman, R. Hintzen","doi":"10.1093/jnen/nlv004","DOIUrl":"https://doi.org/10.1093/jnen/nlv004","url":null,"abstract":"Using proteomics, we previously identified chromogranin A (CgA) and clusterin (CLU) as disease-related proteins in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). CgA and CLU are involved in cell survival and are implicated in neurodegenerative disorders and may also have roles in MS pathophysiology. We investigated CgA and CLU expression in lesions and nonlesional regions in postmortem brains of MS patients and controls and in the brains of marmosets with experimental autoimmune encephalomyelitis. By quantitative PCR, mRNA levels of CgA and CLU were elevated in white matter but not in grey matter of MS patients. In situ analyses showed greater expression of CgA and CLU in white matter lesions than in normal-appearing regions in MS patients and in the marmosets, primarily in or adjacent to perivascular spaces and inflammatory infiltrates. Both proteins were expressed by glial fibrillary acidic protein-positive astrocytes. CgA was more localized in astrocytic processes and endfeet surrounding blood vessels and was abundant in the superficial glia limitans and ependyma, 2 CSF-brain borders. Increased expression of CgA and CLU in reactive astrocytes in MS white matter lesions supports a role for these molecules as neuro-inflammatory mediators and their potential as CSF markers of active pathological processes in MS patients.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":"17 1","pages":"86–98"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84022727","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: 19