Journal of Neuropathology and Experimental Neurology最新文献

The cholinergic basal forebrain and its role in neurodegeneration. 胆碱能基底前脑及其在神经变性中的作用。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-10-06 DOI: 10.1093/jnen/nlaf112

Matthew D Cykowski, Joseph C Masdeu

引用次数: 0

Mapping the expression of endothelial adhesion receptors for Plasmodium falciparum-infected erythrocytes in fatal cerebral malaria in Malawian children. 恶性疟原虫感染的红细胞在马拉维儿童致死性脑疟疾中内皮粘附受体的表达

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-09-24 DOI: 10.1093/jnen/nlaf104

Katerina Dorovini-Zis, Hong Li, Chen Zhe, Bo Zhang, Dylan Small, Terrie E Taylor

{"title":"Mapping the expression of endothelial adhesion receptors for Plasmodium falciparum-infected erythrocytes in fatal cerebral malaria in Malawian children.","authors":"Katerina Dorovini-Zis, Hong Li, Chen Zhe, Bo Zhang, Dylan Small, Terrie E Taylor","doi":"10.1093/jnen/nlaf104","DOIUrl":"https://doi.org/10.1093/jnen/nlaf104","url":null,"abstract":"We investigated the expression and distribution of 5 cytoadhesion receptors for the Plasmodium falciparum erythrocyte membrane protein 1 in 12 regions of post-mortem brains of 50 Malawian children, that is, 27 with the clinical and pathological diagnosis of cerebral malaria (CM) and 23 with a non-malarial cause of death. We quantified the expression of each receptor by microvascular endothelium and the colocalization of receptor-expressing microvessels with sequestered infected red blood cells (iRBC) and calculated a receptor-independent sequestration ratio. There were differences in the level of expression and regional distribution of the five receptors: ICAM-1 was the most widely expressed receptor, followed by CD36, VCAM-1, E-selectin, and thrombospondin. Receptor-expressing microvessels were most numerous in the frontal lobe and least numerous in the brainstem and cerebellum. Colocalization of receptor-expressing endothelial cells with iRBC was present in all brain regions; it was highest for ICAM-1 and CD36 and greatest in the frontal lobe. The sequestration ratios were close to 100% for all receptors across all brain regions and were similar in cerebral and extracerebral microvessels. Receptor expression and colocalization ratios were greater in the brain than in the lung, heart, liver, spleen, and subcutaneous tissue. These differences in cerebral endothelial expression of cytoadhesion receptors and their preferential regional distribution may underpin differences in iRBC sequestration and lesion development in CM. Moreover, greater expression of these receptors in the brain vs peripheral organs may explain a comparatively greater degree of iRBC sequestration in the brain.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137968","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

Occult prostatic adenocarcinoma metastasis to the sphenoid sinus: A case report and literature review. 隐匿性前列腺腺癌向蝶窦转移1例并文献复习。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-09-22 DOI: 10.1093/jnen/nlaf113

Thomas Auen, Michael Punsoni

引用次数: 0

Neuroprotective effects of estradiol and progesterone against hypoxia-induced apoptosis in mouse primary cortical neurons. 雌二醇和黄体酮对小鼠原代皮质神经元缺氧诱导凋亡的神经保护作用。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-09-18 DOI: 10.1093/jnen/nlaf035

Abolfazl Azami Tameh, Javad Amini Mahabadi, Mohammad Ali Atlasi, Cordian Beyer, Zeinab Vahidinia

{"title":"Neuroprotective effects of estradiol and progesterone against hypoxia-induced apoptosis in mouse primary cortical neurons.","authors":"Abolfazl Azami Tameh, Javad Amini Mahabadi, Mohammad Ali Atlasi, Cordian Beyer, Zeinab Vahidinia","doi":"10.1093/jnen/nlaf035","DOIUrl":"https://doi.org/10.1093/jnen/nlaf035","url":null,"abstract":"Hypoxia leads to neuronal damage and 17β-estradiol (E2) and progesterone (P4) exhibit neuroprotective properties in such conditions. However, the precise mechanisms behind these effects remain unexplored. This study evaluates the neuroprotective effects and underlying mechanisms of E2, P4, and their combination (EP) against hypoxic injury. We created a cerebral hypoxia injury model using the hypoxia/reoxygenation (H/R) technique. Primary cortical neurons from 15-day-old mouse embryos were cultured for 7 days. They were then treated with E2, P4, or EP and subsequently subjected to hypoxia. Neurons were identified using MAP2; and neurites and cell bodies were immunolabeled with SMI-311 and SMI-312. Cell viability and damage were assessed by MTS and lactate dehydrogenase assays, apoptosis by PI/Hoechst staining, and cleaved caspase-3 expression by Western blotting. The results showed that most cultured cells were neurons with well-developed neurites. Hypoxia significantly reduced cell viability and increased neuronal death, with elevated caspase-3 expression. Hormone treatments enhanced cell viability and reduced neuronal death. To investigate the potential mechanism, we analyzed the cleaved caspase 3 expression but no significant differences in caspase-3 expression were observed between groups. Overall, hormone therapy alleviated hypoxic injury but did not affect caspase activity. This study provides insights into the neuroprotective mechanisms of hormone therapy.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091973","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

Transthyretin immunohistochemistry on muscle and nerve biopsies detects hereditary and wild-type transthyretin amyloidosis with high sensitivity and specificity. 肌肉和神经活检的甲状腺素免疫组化检测遗传性和野生型甲状腺素淀粉样变性具有高敏感性和特异性。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-09-18 DOI: 10.1093/jnen/nlaf111

Mohamed Elnagdy, Chunyu Cai

引用次数: 0

Mitochondrial dysfunction and its impact on pyroptosis and ferroptosis cross talk in glioma cells. 胶质瘤细胞线粒体功能障碍及其对焦下垂和铁下垂串扰的影响。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-09-17 DOI: 10.1093/jnen/nlaf099

Yunzhu Guo, Hang Liu, Ziqi Gao, Zhengjun Zhou, Yichuan Zhao, Ming Wang, Shenjie Li, Wei Xiang, Jin Liao, Jie Zhou

{"title":"Mitochondrial dysfunction and its impact on pyroptosis and ferroptosis cross talk in glioma cells.","authors":"Yunzhu Guo, Hang Liu, Ziqi Gao, Zhengjun Zhou, Yichuan Zhao, Ming Wang, Shenjie Li, Wei Xiang, Jin Liao, Jie Zhou","doi":"10.1093/jnen/nlaf099","DOIUrl":"https://doi.org/10.1093/jnen/nlaf099","url":null,"abstract":"Glioblastomas (GBM), the most aggressive primary brain tumors, remain challenging to treat due to their rapid proliferation, invasiveness, and resistance to current therapies. Emerging evidence highlights pyroptosis and ferroptosis as critical regulators of tumor progression. This review elucidates the pivotal role of mitochondrial dysfunction in driving these programmed cell death pathways in GBM. Specifically, mitochondrial abnormalities induce overproduction of reactive oxygen species (ROS) and disrupt iron homeostasis, thereby triggering pyroptosis through inflammasome activation and ferroptosis via lipid peroxidation accumulation. Impaired mitochondrial dynamics, such as membrane potential collapse, pro-inflammatory cytokine release, and defective mitophagy, synergistically determine tumor cell fates. We propose novel therapeutic strategies targeting mitochondrial ROS-scavenging systems, iron-sulfur cluster biosynthesis, and mitophagy modulation to overcome resistance to treatment of GBM. These investigations not only advance the understanding of the pathobiology of GBM but also underscore mitochondria as multifaceted therapeutic hubs and offer translational potential for other diseases linked to mitochondrial dysregulation. By integrating cutting-edge research data, this review establishes a foundation for developing precision therapies centered on pyroptosis and ferroptosis modulation, bridging mechanistic discoveries with clinical innovation in neuro-oncology.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091916","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

Activated signaling pathways and metabolic processes in disseminating myxoid glioneuronal tumors. 黏液样胶质细胞肿瘤传播中的激活信号通路和代谢过程。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-09-15 DOI: 10.1093/jnen/nlaf103

William Y Chiang, Xiaoyu Li, Ryuma Tanaka, Jason Chiang

{"title":"Activated signaling pathways and metabolic processes in disseminating myxoid glioneuronal tumors.","authors":"William Y Chiang, Xiaoyu Li, Ryuma Tanaka, Jason Chiang","doi":"10.1093/jnen/nlaf103","DOIUrl":"https://doi.org/10.1093/jnen/nlaf103","url":null,"abstract":"Myxoid glioneuronal tumor (MGNT) is a recently recognized rare neural tumor in the 2021 WHO Classification of CNS Tumors. Myxoid glioneuronal tumor has low-grade histology and a generally good overall survival rate. However, some tumors exhibit leptomeningeal or intraventricular dissemination at presentation or during disease progression and the underlying biology is unknown. Finding activated signaling pathways and metabolic processes in disseminating MGNTs may reveal potential therapy targets for disseminated tumors. We compared the DNA methylome and transcriptome of disseminating (n = 4) and non-disseminating (n = 7) MGNTs to identify differentially methylated regions and differentially expressed genes. Gene set enrichment analysis (GSEA) was used to identify associated specific signaling and metabolic pathway activation. Myxoid glioneuronal tumors showed similar DNA methylome profiles regardless of dissemination status. Transcription factor MSX1 activation was found in disseminating MGNTs at the transcriptome level. Gene set enrichment analysis revealed the activation of the MAPK, PI3K/AKT/mTOR, MYC, and RAS pathways, as well as multiple metabolic pathways, including OXPHOS, translation, and cell cycle pathways, in disseminating MGNTs. In summary, disseminating MGNT shows simultaneous activation of multiple signaling and metabolic pathways, which may serve as potential therapeutic targets for disseminated disease.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091838","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

Convolutional neural network-derived neurofibrillary tangle classifiers: Investigative tools to identify maturation levels and explore post-translational modifications using laser capture microdissection coupled mass spectrometry. 卷积神经网络衍生的神经原纤维缠结分类器：使用激光捕获显微解剖耦合质谱法识别成熟水平和探索翻译后修饰的研究工具。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-09-14 DOI: 10.1093/jnen/nlaf108

Couger Jimenez Jaramillo, Drew Nedderman, Erpan Ahat, John L McElwee, Michael Soper, Darryl Ballard, Ling Zhang, Kelly M Credille, Gary Heady, Eric D Hsi, Michael E Hodsdon, Timothy R Holzer, Aaron M Gruver, William T Harrison

{"title":"Convolutional neural network-derived neurofibrillary tangle classifiers: Investigative tools to identify maturation levels and explore post-translational modifications using laser capture microdissection coupled mass spectrometry.","authors":"Couger Jimenez Jaramillo, Drew Nedderman, Erpan Ahat, John L McElwee, Michael Soper, Darryl Ballard, Ling Zhang, Kelly M Credille, Gary Heady, Eric D Hsi, Michael E Hodsdon, Timothy R Holzer, Aaron M Gruver, William T Harrison","doi":"10.1093/jnen/nlaf108","DOIUrl":"https://doi.org/10.1093/jnen/nlaf108","url":null,"abstract":"Post-translational modifications (PTM) of tau are implicated in Alzheimer disease (AD) progression and are established biomarkers in cerebrospinal fluid and plasma; however, the labor-intensive nature of conventional proteomics limits their investigation in histology-specific contexts. We describe the findings of an artificial intelligence-guided laser capture microdissection (LCM) pipeline for harvesting neurofibrillary tangles (NFTs) by maturation level into pretangles (pre-NFTs), mature tangles (iNFTs), and ghost tangles (eNFTs) using 38 cases obtained from 2 independent biobanks. We evaluated the performance characteristics of proprietary machine learning algorithms for the subclassification of these NFT categories in anti-pTau217-stained whole slide images of entorhinal cortex, hippocampus, frontal, and parietal cortex sections. Overall precision/recall/F1 scores were highest for Classifier A (0.6/0.46/0.5). The best performing algorithm was used to guide LCM capture and inform NFT enrichment. Targeted proteomics on tau signature peptides (pTau181, pTau217, and TauMTBR) was performed on approximately 1250 NFT collections. The results demonstrated that their abundance increased from pretangles to mature tangles (∼2-11-fold increase), and that this was followed by a sharp reduction in ghost tangles (∼3-116-fold decrease), with pTau217 showing the most drastic change. Pathologist-trained NFT classifiers represent an objective albeit imperfect means to enrich specific morphologic forms permitting coupled LCM-MS (mass spectrometry) to investigate AD-associated PTM.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091930","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

Increased efficacy of adipose-derived mesenchymal stem cells transduced with klotho in differentiation and maturation of oligodendrocytes in a mouse model of experimental autoimmune encephalomyelitis. 在实验性自身免疫性脑脊髓炎小鼠模型中，klotho转导的脂肪源性间充质干细胞在少突胶质细胞分化和成熟中的作用增强。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-09-13 DOI: 10.1093/jnen/nlaf095

Maryam Rezapour Kalkhoran, Narges Maleki, Fatemeh Rahbarizadeh, Abdolamir Allameh

{"title":"Increased efficacy of adipose-derived mesenchymal stem cells transduced with klotho in differentiation and maturation of oligodendrocytes in a mouse model of experimental autoimmune encephalomyelitis.","authors":"Maryam Rezapour Kalkhoran, Narges Maleki, Fatemeh Rahbarizadeh, Abdolamir Allameh","doi":"10.1093/jnen/nlaf095","DOIUrl":"https://doi.org/10.1093/jnen/nlaf095","url":null,"abstract":"Current therapies for multiple sclerosis (MS) exert immunomodulatory effects but do not directly repair central nervous system (CNS) damage. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic strategy for MS, as they have been shown to promote myelin repair. Genetic modifications of MSCs have been reported to enhance their therapeutic efficiency in neurodegenerative diseases. This study aimed to investigate the therapeutic potential of MSCs engineered with secreted klotho (s-KL) in enhancing remyelination by mature oligodendrocytes in an experimental autoimmune encephalomyelitis (EAE) model in mice. The results showed that MSCs carrying s-KL alleviated clinical signs and reduced inflammation and demyelination in the CNS more significantly than MSCs. Compared to MSCs, s-KL MSCs also exhibited an enhanced capacity for differentiation and maturation of oligodendrocytes, as demonstrated by increased mRNA and protein expression of Olig2 and Nogo-A in the CNS of mice with EAE. These findings indicate that overexpression of s-KL enhances the therapeutic potential of MSCs to induce remyelination and may represent a novel approach to improve the efficacy of stem cell-based therapy in MS.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091927","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

Aqueductal posterior fossa type B ependymoma in Li-Fraumeni syndrome. Li-Fraumeni综合征中的输水管后窝B型室管膜瘤。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-09-12 DOI: 10.1093/jnen/nlaf100

Yoshitaka Mizushima, Kohei Fukuoka, Kayoko Ichimura, Daiju Oba, Mamoru Honda, Yuichi Mitani, Koichi Oshima, Makiko Mori, Yuki Arakawa, Hirofumi Ohashi, Yutaka Tanami, Koichi Ichimura, Kaishi Satomi, Junko Hirato, Atsuko Nakazawa, Jun Kurihara, Katsuyoshi Koh

引用次数: 0