Journal of Neuropathology and Experimental Neurology最新文献_第8页

Long survival in a patient with fumarate hydratase mutation-associated glioma. 富马酸氢化酶突变相关胶质瘤患者的长期存活。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae100

Regina R Reimann, Dorothee Gramatzki, Andrea Bink, Jürgen Hench, Stephan Frank, Martina Haberecker, Tibor Hortobagyi, Kristof Egervari, Doron Merkler, Kenneth Aldape, Michael Weller

引用次数: 0

Potential of the pharmacological inhibition of CCL2-CCR2 axis via targeting FROUNT to prevent the initiation and the progression of intracranial aneurysms in rats. 通过靶向 FROUNT 对 CCL2-CCR2 轴进行药理抑制以预防大鼠颅内动脉瘤的发生和发展的潜力。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae115

Isao Ono, Masahiko Itani, Akihiro Okada, Akitsugu Kawashima, Etsuko Toda, Yoshiki Arakawa, Yuya Terashima, Tomohiro Aoki

{"title":"Potential of the pharmacological inhibition of CCL2-CCR2 axis via targeting FROUNT to prevent the initiation and the progression of intracranial aneurysms in rats.","authors":"Isao Ono, Masahiko Itani, Akihiro Okada, Akitsugu Kawashima, Etsuko Toda, Yoshiki Arakawa, Yuya Terashima, Tomohiro Aoki","doi":"10.1093/jnen/nlae115","DOIUrl":"10.1093/jnen/nlae115","url":null,"abstract":"Intracranial aneurysms (IAs) affect 1%-5% of the public and are a major cause of subarachnoid hemorrhage. Currently, there is no medical treatment to prevent the progression or rupture of IAs. Recent studies have defined IA as a chronic inflammatory disease in which macrophages infiltrate intracranial arteries via the CCL2-CCR2 axis. The chemokine signal regulator FROUNT mediates this axis, and it can be inhibited by the anti-alcoholism drug disulfiram. Therefore, inhibition of macrophage infiltration by interfering with FROUNT using disulfiram may represent a strategy to prevent exacerbation of IAs. Here, effects of disulfiram were investigated in vitro and in an animal model of IAs. FROUNT expression was observed on infiltrated macrophages both in human IAs and in the rat IA model by immunohistochemistry. In vitro treatment with disulfiram suppressed CCL2-mediated migration of cultured rat macrophages in a transwell system. Disulfiram administered in a rat model of IAs inhibited both the initiation and the enlargement of IAs in a dose-dependent manner; this was accompanied by suppression of macrophage infiltration. These results suggest that pharmacological inhibition of the CCL2-CCR2-FROUNT signaling cascade could be a treatment of patients with IAs.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"132-140"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682047","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

Clinical and neuropathological analysis of Down syndrome over 7 decades of life. 唐氏综合征 70 年来的临床和神经病理学分析。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae110

Sonal Sukreet, Vanessa S Goodwill, Jennifer Ngolab, Ha Y Kim, Solana Leisher, Sahar Salehi, Michael S Rafii, Annie Hiniker, Robert A Rissman

引用次数: 0

Tumor microtubes: A new potential therapeutic target for high-grade gliomas. 肿瘤微管：高级别胶质瘤的潜在治疗新靶点

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae119

Yunzhu Guo, Yangxin Li, Peng Su, Min Yan, Ming Wang, Shenjie Li, Wei Xiang, Ligang Chen, Wei Dong, Zhengjun Zhou, Jie Zhou

{"title":"Tumor microtubes: A new potential therapeutic target for high-grade gliomas.","authors":"Yunzhu Guo, Yangxin Li, Peng Su, Min Yan, Ming Wang, Shenjie Li, Wei Xiang, Ligang Chen, Wei Dong, Zhengjun Zhou, Jie Zhou","doi":"10.1093/jnen/nlae119","DOIUrl":"10.1093/jnen/nlae119","url":null,"abstract":"High-grade infiltrating gliomas are highly aggressive and fatal brain tumors that present significant challenges for research and treatment due to their complex microenvironment and tissue structure. Recent discovery of tumor microtubes (TMs) has provided new insights into how high-grade gliomas develop in the brain and resist treatment. TMs are unique, ultra-long, and highly functional membrane protrusions that form multicellular networks and play crucial roles in glioma invasiveness, drug resistance, recurrence, and heterogeneity. This review focuses on the different roles that TMs play in glioma cell communication, material transport, and tumor cell behavior. Specifically, non-connecting TMs primarily promote glioma invasiveness, likely related to their role in enhancing cell motility. On the other hand, interconnecting TMs form functional and communication networks by connecting with surrounding astrocytes and neurons, thereby promoting glioma malignancy. We summarize the factors that influence the formation of TMs in gliomas and current strategies targeting TMs. As the understanding of TMs advances, we are closer to uncovering whether they might be the long-sought Achilles' heel of treatment-resistant gliomas. By delving deeper into TMs research, we hope to develop more effective therapeutic strategies for patients with malignant gliomas.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"93-103"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668337","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

Detection of Gram-positive and Gram-negative bacteria in brain abscesses by 16S rRNA in situ hybridization. 利用 16S rRNA 原位杂交技术检测脑脓肿中的革兰氏阳性和革兰氏阴性细菌。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae118

William Mbongo, Alvaro C Laga, Isaac H Solomon

{"title":"Detection of Gram-positive and Gram-negative bacteria in brain abscesses by 16S rRNA in situ hybridization.","authors":"William Mbongo, Alvaro C Laga, Isaac H Solomon","doi":"10.1093/jnen/nlae118","DOIUrl":"10.1093/jnen/nlae118","url":null,"abstract":"In situ hybridization (ISH) staining of bacterial 16S ribosomal RNA (rRNA) is an alternative to standard histological stains (eg, Gram, Warthin-Starry), and may improve the diagnosis of bacterial brain abscesses. To evaluate the utility of 16S rRNA ISH, a 10-year retrospective cohort was assembled from a large academic medical center. Results of histological stains, cultures, and 16S rRNA sequencing were extracted from reports, and new Gram and 16S rRNA ISH stains were performed. Histologically identifiable bacteria were present in 40/63 (63%) cases and 38/57 (67%) were associated with positive cultures. Overall, 16S rRNA ISH was positive in 18/63 (29%) cases, including 16/37 (43%) with positive Gram stains, 12/38 (32%) positive by culture, and 4/8 (50%) positive by sequencing. 16S rRNA ISH highlighted bacteria in 14/40 (35%) cases with Gram-positive organisms and 9/17 (53%) with Gram-negative organisms (including 6 polymicrobial cases). Compared to a composite gold standard of Gram stain and culture, the sensitivity and specificity of 16S rRNA ISH were 35% and 93%, respectively. While sensitivity is relatively low, 16S rRNA ISH may be useful for distinguishing real organisms from artifacts and for identifying brain abscess cases suitable for 16S rRNA sequencing.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"141-146"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605042","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

A machine learning approach to automate microinfarct and microhemorrhage screening in hematoxylin and eosin-stained human brain tissues. 机器学习方法在苏木精和伊红染色的人脑组织中自动筛选微梗死和微出血。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae120

Luca Cerny Oliveira, Joohi Chauhan, Ajinkya Chaudhari, Sen-Ching S Cheung, Viharkumar Patel, Amparo C Villablanca, Lee-Way Jin, Charles DeCarli, Chen-Nee Chuah, Brittany N Dugger

{"title":"A machine learning approach to automate microinfarct and microhemorrhage screening in hematoxylin and eosin-stained human brain tissues.","authors":"Luca Cerny Oliveira, Joohi Chauhan, Ajinkya Chaudhari, Sen-Ching S Cheung, Viharkumar Patel, Amparo C Villablanca, Lee-Way Jin, Charles DeCarli, Chen-Nee Chuah, Brittany N Dugger","doi":"10.1093/jnen/nlae120","DOIUrl":"10.1093/jnen/nlae120","url":null,"abstract":"Microinfarcts and microhemorrhages are characteristic lesions of cerebrovascular disease. Although multiple studies have been published, there is no one universal standard criteria for the neuropathological assessment of cerebrovascular disease. In this study, we propose a novel application of machine learning in the automated screening of microinfarcts and microhemorrhages. Utilizing whole slide images (WSIs) from postmortem human brain samples, we adapted a patch-based pipeline with convolutional neural networks. Our cohort consisted of 22 cases from the University of California Davis Alzheimer's Disease Research Center brain bank with hematoxylin and eosin-stained formalin-fixed, paraffin-embedded sections across 3 anatomical areas: frontal, parietal, and occipital lobes (40 WSIs with microinfarcts and/or microhemorrhages, 26 without). We propose a multiple field-of-view prediction step to mitigate false positives. We report screening performance (ie, the ability to distinguish microinfarct/microhemorrhage-positive from microinfarct/microhemorrhage-negative WSIs), and detection performance (ie, the ability to localize the affected regions within a WSI). Our proposed approach improved detection precision and screening accuracy by reducing false positives thereby achieving 100% screening accuracy. Although this sample size is small, this pipeline provides a proof-of-concept for high efficacy in screening for characteristic brain changes of cerebrovascular disease to aid in screening of microinfarcts/microhemorrhages at the WSI level.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"114-125"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895599","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

Hippocampal dentate gyrus dysplasia and the risk of sudden unexpected death. 海马齿状回发育不良与意外猝死的风险

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae121

Douglas C Miller, Kristen M Scheitler, Jeffery Holloway, C Christopher Stacy

{"title":"Hippocampal dentate gyrus dysplasia and the risk of sudden unexpected death.","authors":"Douglas C Miller, Kristen M Scheitler, Jeffery Holloway, C Christopher Stacy","doi":"10.1093/jnen/nlae121","DOIUrl":"10.1093/jnen/nlae121","url":null,"abstract":"Hippocampal dentate gyral dysplasia is well-described in temporal lobe epilepsy and may be a risk factor for sudden, unexpected death in several populations: infants (sudden infant death syndrome [SIDS], sudden unexpected infant death [SUID]), toddlers (sudden unexpected death of a child [SUDC]), and epileptics (sudden unexpected death in epilepsy [SUDEP]). We examined reports and histopathological slides from autopsies performed at our institution from 2008 through 2016 to determine whether the presence or absence of any of the described forms of such dysplasias (duplications, hyperconvolutions, and granule cell dispersion, including bilamination), correlated with the causes of death. From well over 4000 autopsies, we identified 949 autopsies with a neuropathology examination by a neuropathologist. Of these, 205 cases (21.6%) had 1 or more of the described abnormalities of 1 or both dentate gyri; 87 (42.4%) of the individuals in this group of 205 autopsies had died suddenly and unexpectedly, including 29/90 (32.2%) cases of SUDEP, 17/31 (54.8%) cases of SUDC, and 51/104 (49.0%) cases of infants with SIDS or SUID. We conclude that these changes are readily recognizable by experienced neuropathologists and that because they are overrepresented in an autopsy population that died suddenly and unexpectedly, they may represent a risk factor for such outcomes.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"126-131"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710568","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

Deep learning-based classifier for carcinoma of unknown primary using methylation quantitative trait loci. 基于甲基化数量性状位点的未知原发癌深度学习分类器。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae123

Adam Walker, Camila S Fang, Chanel Schroff, Jonathan Serrano, Varshini Vasudevaraja, Yiying Yang, Sarra Belakhoua, Arline Faustin, Christopher M William, David Zagzag, Sarah Chiang, Andres Martin Acosta, Misha Movahed-Ezazi, Kyung Park, Andre L Moreira, Farbod Darvishian, Kristyn Galbraith, Matija Snuderl

{"title":"Deep learning-based classifier for carcinoma of unknown primary using methylation quantitative trait loci.","authors":"Adam Walker, Camila S Fang, Chanel Schroff, Jonathan Serrano, Varshini Vasudevaraja, Yiying Yang, Sarra Belakhoua, Arline Faustin, Christopher M William, David Zagzag, Sarah Chiang, Andres Martin Acosta, Misha Movahed-Ezazi, Kyung Park, Andre L Moreira, Farbod Darvishian, Kristyn Galbraith, Matija Snuderl","doi":"10.1093/jnen/nlae123","DOIUrl":"10.1093/jnen/nlae123","url":null,"abstract":"Cancer of unknown primary (CUP) constitutes between 2% and 5% of human malignancies and is among the most common causes of cancer death in the United States. Brain metastases are often the first clinical presentation of CUP; despite extensive pathological and imaging studies, 20%-45% of CUP are never assigned a primary site. DNA methylation array profiling is a reliable method for tumor classification but tumor-type-specific classifier development requires many reference samples. This is difficult to accomplish for CUP as many cases are never assigned a specific diagnosis. Recent studies identified subsets of methylation quantitative trait loci (mQTLs) unique to specific organs, which could help increase classifier accuracy while requiring fewer samples. We performed a retrospective genome-wide methylation analysis of 759 carcinoma samples from formalin-fixed paraffin-embedded tissue samples using Illumina EPIC array. Utilizing mQTL specific for breast, lung, ovarian/gynecologic, colon, kidney, or testis (BLOCKT) (185k total probes), we developed a deep learning-based methylation classifier that achieved 93.12% average accuracy and 93.04% average F1-score across a 10-fold validation for BLOCKT organs. Our findings indicate that our organ-based DNA methylation classifier can assist pathologists in identifying the site of origin, providing oncologists insight on a diagnosis to administer appropriate therapy, improving patient outcomes.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"147-154"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751146","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

New criteria to predict LATE-NC in the clinical setting: Probable/Possible LATE and LANS. 在临床环境中预测 LATE-NC 的新标准：可能/可能的 LATE 和 LANS。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-01-01 DOI: 10.1093/jnen/nlae113

Peter T Nelson

引用次数: 0

Focal granule cell bilamination of the dentate gyrus-its prevalence across the human age spectrum and review of the literature. 齿状回局灶性颗粒细胞淤积症--在人类各年龄段的发病率及文献综述。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-01-01 DOI: 10.1093/jnen/nlae109

Rita Machaalani, Michael Rodriguez, Arunnjah Vivekanandarajah

{"title":"Focal granule cell bilamination of the dentate gyrus-its prevalence across the human age spectrum and review of the literature.","authors":"Rita Machaalani, Michael Rodriguez, Arunnjah Vivekanandarajah","doi":"10.1093/jnen/nlae109","DOIUrl":"10.1093/jnen/nlae109","url":null,"abstract":"The prevalence of focal granule cell bilamination (FGCB) in the hippocampal dentate gyrus varies from 0% to 44%, depending on age and study population. FGCB is commonly thought to be a specific feature of temporal lobe epilepsy (TLE) but its prevalence in cases without TLE is unclear. Using formalin-fixed, paraffin-embedded hippocampal sections, this retrospective postmortem study evaluated the prevalence of FGCB and other granule cell pathologies in infants (1-12 months of age, n = 16), children (4-10 years, n = 6), and adults (28-91 years, n = 15) with no known history of epilepsy or seizures. We found FGCB in 6% of infants, 17% of children, and 27% of adults. We then compared our findings with those in published reports of sudden unexpected deaths in infancy (SUDI), childhood (SUDC), and epilepsy (SUDEP), and in surgical specimens from patients with TLE. The reported prevalence of FGCB in those studies was 6%-19% in infants, 0%-17% in children, and 0%-2% in adults in non-seizure-related cases and 9% in children and 3%-25% in adults with TLE. Our findings highlight the presence of FGCB in individuals with no known epilepsy/seizure-related histories in proportions similar to those reported in individuals with clinical epilepsy.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"22-33"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522195","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