Journal of Neuropathology and Experimental Neurology最新文献_第7页

Cortical variant multiple sclerosis presenting clinically as Lewy body dementia. 皮质变异性多发性硬化，临床表现为路易体痴呆。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-03-06 DOI: 10.1093/jnen/nlaf015

Delaney Liskey, Alexia R Maier, Shunsuke Koga, Sarosh Irani, Neill Graff-Radford, Keith A Josephs, Dennis W Dickson, Shanu F Roemer

引用次数: 0

Insights in the underlying pathophysiology of brain malformations associated with VRK1-related syndrome derived from fetal neuropathology. 胎儿神经病理学衍生的vrk1相关综合征相关脑畸形的潜在病理生理学研究。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-03-06 DOI: 10.1093/jnen/nlaf014

Aude Tessier, Olivier Monestier, François Guillaume Debray, Fréderic Vauthier, Valerie Benoit, Kim Van Berkel, Leila Ghassemi, Stefanie Brock

引用次数: 0

Acquired intradiploic epidermoid cyst: A rare case report with literature review. 后天性腹膜内表皮样囊肿：罕见病例报告及文献综述

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-21 DOI: 10.1093/jnen/nlae106

Jacob A Schroeder, Mohammed Sabawi, Amr H Masaadeh, Kathryn L Eschbacher, Nitesh Shekhrajka, Márcio Luís Duarte, Leonardo Furtado Freitas

引用次数: 0

An analysis of RNA quality metrics in human brain tissue. 人脑组织中RNA质量指标的分析。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-21 DOI: 10.1093/jnen/nlae132

Jiahe Tian, Tiffany G Lam, Sophie K Ross, Benjamin Ciener, Sandra Leskinen, Sharanya Sivakumar, David A Bennett, Vilas Menon, Guy M McKhann, Alexi Runnels, Andrew F Teich

{"title":"An analysis of RNA quality metrics in human brain tissue.","authors":"Jiahe Tian, Tiffany G Lam, Sophie K Ross, Benjamin Ciener, Sandra Leskinen, Sharanya Sivakumar, David A Bennett, Vilas Menon, Guy M McKhann, Alexi Runnels, Andrew F Teich","doi":"10.1093/jnen/nlae132","DOIUrl":"10.1093/jnen/nlae132","url":null,"abstract":"Human brain tissue studies have used a range of metrics to assess RNA quality but there are few large-scale cross-comparisons of presequencing quality metrics with RNA-seq quality. We analyzed how postmortem interval (PMI) and RNA integrity number (RIN) before RNA-seq relate to RNA quality after sequencing (percent of counts in top 10 genes [PTT], 5' bias, and 3' bias), and with individual gene counts across the transcriptome. We analyzed 4 human cerebrocortical tissue sets (1 surgical, 3 autopsy), sequenced with varying protocols. Postmortem interval and RIN had a low inverse correlation (down to r = -0.258, P < .001 across the autopsy cohorts); both PMI and RIN showed consistent and opposing correlations with PTT (up to r = 0.215, P < .001 for PMI and down to r = -0.677, P < .001 for RIN across the autopsy cohorts). Unlike PMI, RIN showed consistent correlations with measurements of 3' and 5' bias in autopsies (r = -0.366, P < .001 with 3' bias). RNA integrity number correlated with 3933 genes across the 4 datasets vs 138 genes for PMI. Neuronal and immune response genes correlated positively and negatively with RIN, respectively. Thus, different gene sets have divergent relationships with RIN. These analyses suggest that conventional metrics of RNA quality have varying values and that PMI has an overall modest effect on RNA quality.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"236-243"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Detection of rare and novel gene fusions in patients with diffuse glioma: An institutional retrospective study. 弥漫性胶质瘤患者罕见和新型基因融合的检测：一项机构回顾性研究。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-21 DOI: 10.1093/jnen/nlae105

Kentaro Ohara, Majd Al Assaad, Samantha N McNulty, Hussein Alnajar, Andrea Sboner, David C Wilkes, Feng He, Jenny Zhaoying Xiang, Susan Mathew, Olivier Elemento, David J Pisapia, Juan Miguel Mosquera

引用次数: 0

Mesencephalosynapsis and aqueductal stenosis. 中脑突触和导水管狭窄。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-21 DOI: 10.1093/jnen/nlae128

Yael Fisher, Patrick Shannon, Orli Greenberg, David Chitayat, Karen Chong, Susan Blaser, Shiri Shinar

{"title":"Mesencephalosynapsis and aqueductal stenosis.","authors":"Yael Fisher, Patrick Shannon, Orli Greenberg, David Chitayat, Karen Chong, Susan Blaser, Shiri Shinar","doi":"10.1093/jnen/nlae128","DOIUrl":"10.1093/jnen/nlae128","url":null,"abstract":"Mesencephalosynapsis is characterized by a failure of the dorsal brainstem colliculi to separate into distinct lateral masses (non-cleavage, a.k.a. \"fusion\"). It is linked to ventriculomegaly and aqueductal stenosis but other associations have not been systematically examined. We reviewed a large cohort of fetal hydrocephalus cases to explore associations of aqueductal stenosis, mesencephalosynapsis, and other pathologies. Among 115 cases of fetal obstructive hydrocephalus (15-41 weeks gestation), mesencephalosynapsis was seen in 44 cases (38.3%). We graded the wide range of abnormal aqueductal histology; mesencephalosynapsis was associated with 67% of severe, 35% of mild, and 10% of borderline aqueductal pathologies. In 75% of cases, it was associated with other CNS anomalies, including rhombencephalosynapsis, holoprosencephaly, hemifacial microsomia, and amniotic rupture sequence. We also identified 2 cases of aqueductal stenosis associated with brainstem tegmental injury, probably ischemic in origin, without mesencephalosynapsis. Clinical and genetic associations of mesencephalosynapsis included diabetic embryopathy, amniotic rupture sequence, chromosomal abnormalities, and mutations in TBCD132, FRAS1, and NECTIN1. This is the largest review of the histology of fetal aqueductal stenosis to date. We conclude that mesencephalosynapsis points to a defect in embryonic brainstem patterning and may be isolated, associated with other malformations, and that it is found in heritable and non-heritable conditions.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"195-209"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanisms of fibrinogen trans-activation of the EGFR/Ca2+ signaling axis to regulate mitochondrial transport and energy transfer and inhibit axonal regeneration following cerebral ischemia. 纤维蛋白原转激活表皮生长因子受体/Ca2+信号轴调节线粒体转运和能量转移并抑制脑缺血后轴突再生的机制。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-21 DOI: 10.1093/jnen/nlae114

Shengqiang Zhou, Bo Li, Dahua Wu, Yanjun Chen, Wen Zeng, Jia Huang, Lingjuan Tan, Guo Mao, Fang Liu

{"title":"Mechanisms of fibrinogen trans-activation of the EGFR/Ca2+ signaling axis to regulate mitochondrial transport and energy transfer and inhibit axonal regeneration following cerebral ischemia.","authors":"Shengqiang Zhou, Bo Li, Dahua Wu, Yanjun Chen, Wen Zeng, Jia Huang, Lingjuan Tan, Guo Mao, Fang Liu","doi":"10.1093/jnen/nlae114","DOIUrl":"10.1093/jnen/nlae114","url":null,"abstract":"Ischemic stroke results in inhibition of axonal regeneration but the roles of fibrinogen (Fg) in neuronal signaling and energy crises in experimental stroke are under-investigated. We explored the mechanism of Fg modulation of axonal regeneration and neuronal energy crisis after cerebral ischemia using a permanent middle cerebral artery occlusion (MCAO) rat model and primary cortical neurons under low glucose-low oxygen. Behavioral tests assessed neurological deficits; immunofluorescence, immunohistochemistry, and Western-blot analyzed Fg and protein levels. Fluo-3/AM fluorescence measured free Ca2+ and ATP levels were gauged via specific assays and F560nm/F510nm ratio calculations. Mito-Tracker Green labeled mitochondria and immunoprecipitation studied protein interactions. Our comprehensive study revealed that Fg inhibited axonal regeneration post-MCAO as indicated by reduced GAP43 expression along with elevated free Ca2+, both suggesting an energy crisis. Fg impeded mitochondrial function and mediated impairment through the EGFR/Ca2+ axis by trans-activating EGFR via integrin αvβ3 interaction. These results indicate that the binding of Fg with integrin αvβ3 leads to the trans-activation of the EGFR/Ca2+ signaling axis thereby disrupting mitochondrial energy transport and axonal regeneration and exacerbating the detrimental effects of ischemic neuronal injury.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"210-222"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NOD-like receptor X1 promotes autophagy and inactivates NLR family pyrin domain containing 3 inflammasome signaling by binding autophagy-related gene 5 to alleviate cerebral ischemia/reperfusion-induced neuronal injury. nod样受体X1通过结合自噬相关基因5，促进自噬，灭活NLR家族pyrin结构域3炎性小体信号，减轻脑缺血再灌注诱导的神经元损伤。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-21 DOI: 10.1093/jnen/nlae129

Yufen Peng, Yong Long, Chenyi Wan

{"title":"NOD-like receptor X1 promotes autophagy and inactivates NLR family pyrin domain containing 3 inflammasome signaling by binding autophagy-related gene 5 to alleviate cerebral ischemia/reperfusion-induced neuronal injury.","authors":"Yufen Peng, Yong Long, Chenyi Wan","doi":"10.1093/jnen/nlae129","DOIUrl":"10.1093/jnen/nlae129","url":null,"abstract":"Ischemic strokes pose serious risks to human health. We aimed to elucidate the function of NOD-like receptor X1 (NLRX1) in a rat middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injury (CIRI) model and in an oxygen-glucose deprivation/reperfusion (OGD/R)-treated human microglial cell line (HMC3) model. Following NLRX1 upregulation, infarct volumes were measured with 2,3,5-triphenyltetrazolium chloride staining and pathological examination was conducted with hematoxylin-eosin staining. Results suggested that levels of NLRX1 were decreased in brain tissue of MCAO rats and in OGD/R-stimulated HMC3 cells. NOD-like receptor X1 overexpression mitigated the neuronal damage, reduced tumor necrosis factor-α and interleukin-6 expression, alleviated microglial activation, and induced autophagy in vivo and in vitro. Additionally, a coimmunoprecipitation assay indicated that NLRX1 bound to autophagy-related gene 5 (ATG5) to elevate ATG5 expression in HMC3 cells. Further, the elevated NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD, and cleaved caspase 1 expression in MCAO rats and HMC3 cells with OGD/R induction was reduced after NLRX1 upregulation. Importantly, ATG5 depletion abrogated the effects of NLRX1 elevation on NLRP3 inflammasome signaling. These results indicate that NLRX1 promotes autophagy and inactivates NLRP3 inflammasome signaling by binding ATG5 in experimental cerebral ischemia. These data may help the development of novel therapeutic strategies for ischemic stroke.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"223-235"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrating molecular analyses with the 2021 WHO classification of adult pilocytic astrocytomas. 整合分子分析与2021年WHO成人毛细胞星形细胞瘤的分类。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-21 DOI: 10.1093/jnen/nlae130

Beatriz Moreno-Torres, Irene Manzano-Benito, Diana Cantero, Ángel Romo, Ángel Rodríguez de Lope, Manuela Mollejo, Aurelio Hernández-Laín, Bárbara Meléndez

{"title":"Integrating molecular analyses with the 2021 WHO classification of adult pilocytic astrocytomas.","authors":"Beatriz Moreno-Torres, Irene Manzano-Benito, Diana Cantero, Ángel Romo, Ángel Rodríguez de Lope, Manuela Mollejo, Aurelio Hernández-Laín, Bárbara Meléndez","doi":"10.1093/jnen/nlae130","DOIUrl":"10.1093/jnen/nlae130","url":null,"abstract":"Pilocytic astrocytomas (PAs) are benign grade 1 gliomas according to the World Health Organization (WHO). They are common in children but rare in adults in whom they may have a worse prognosis. Pediatric PAs are usually associated with dysregulation of the mitogen-activated protein kinase (MAPK) pathway, often involving BRAF alterations such as the KIAA1549::BRAF (K-B) fusion or V600E mutation. We investigated the molecular characteristics of adult PA using gene-targeted next-generation sequencing and specific gene tests, including for K-B fusion, TERT promoter, and FGFR1 hotspot mutations. The most frequent molecular alterations detected involved the MAPK pathway, particularly affecting BRAF and NF1 genes (55%). The prevalence of the K-B fusion (>40%) was higher than previously reported, likely due to challenges in detecting it. We identified molecular alterations in some cases that raised the differential diagnosis of other tumor types, revealing limitations in the 2021 WHO classification for adult PA. After removing other diagnostic types that may mimic PA histology, no adult patients with a diagnosis of PA and K-B fusion died after more than 10 years of mean follow-up. These findings suggest that, similar to pediatric cases, PA in adults may be driven by a single molecular hit, where the K-B fusion is not related to poor outcome.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"255-263"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unraveling the clinical-pathological correlations of subjects with isolated and mixed neurodegenerative processes in the National Alzheimer's Coordinating Center dataset. 在国家阿尔茨海默氏症协调中心数据集中，揭示具有孤立和混合神经退行性过程的受试者的临床病理相关性。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-21 DOI: 10.1093/jnen/nlae134

Satomi Hiya, Carolina Maldonado-Díaz, Susan K Rohde, Mitzi M Gonzales, Leyla Canbeldek, Lakshmi S Kulumani Mahadevan, Raquel T Yokoda, A Campbell Sullivan, Alicia S Parker, Charles L White, Elena V Daoud, Victoria Flores-Almazan, John F Crary, Kurt Farrell, Jamie M Walker, Timothy E Richardson

{"title":"Unraveling the clinical-pathological correlations of subjects with isolated and mixed neurodegenerative processes in the National Alzheimer's Coordinating Center dataset.","authors":"Satomi Hiya, Carolina Maldonado-Díaz, Susan K Rohde, Mitzi M Gonzales, Leyla Canbeldek, Lakshmi S Kulumani Mahadevan, Raquel T Yokoda, A Campbell Sullivan, Alicia S Parker, Charles L White, Elena V Daoud, Victoria Flores-Almazan, John F Crary, Kurt Farrell, Jamie M Walker, Timothy E Richardson","doi":"10.1093/jnen/nlae134","DOIUrl":"10.1093/jnen/nlae134","url":null,"abstract":"Although Alzheimer disease neuropathologic change (ADNC) is the most common pathology underlying clinical dementia, the presence of multiple comorbid neuropathologies is increasingly being recognized as a major contributor to the worldwide dementia burden. We analyzed 1051 subjects with specific combinations of isolated and mixed pathologies and conducted multivariate logistic regression analysis on a cohort of 4624 cases with mixed pathologies to systematically explore the independent cognitive contributions of each pathology. Alzheimer disease neuropathologic change and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) were both associated with a primary clinical diagnosis of Alzheimer disease (AD) and were characterized by an amnestic dementia phenotype, while only ADNC associated with logopenic variant primary progressive aphasia (PPA). In subjects with ADNC and comorbid LATE-NC, Lewy body disease, and/or cerebrovascular disease, the clinical phenotype was usually diagnosed during life as \"Probable AD.\" Conversely, the combination of ADNC with frontotemporal lobar degeneration with TDP-43, progressive supranuclear palsy (PSP), or corticobasal degeneration (CBD) resulted in a mixed clinical picture, with variable features of amnestic dementia, PPA subtypes, behavioral variant FTD, PSP syndrome, and CBD syndrome. These findings elucidate the cumulative effects of mixed pathologies and provide insights into interactions between neurodegenerative pathologies contributing to a variety of clinical dementia presentations.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"177-194"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0