Journal of Neuropathology and Experimental Neurology最新文献_第2页

CD4+ T-lymphocytes in human saccular intracranial aneurysm walls are associated with aneurysm rupture. 人囊状颅内动脉瘤壁上CD4+ t淋巴细胞与动脉瘤破裂有关。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-06-11 DOI: 10.1093/jnen/nlaf060

Nora Firtser, Eliisa Netti, Eliisa Kekäläinen, Satu Lehti, Petri T Kovanen, Mika Niemelä, Riikka Tulamo

{"title":"CD4+ T-lymphocytes in human saccular intracranial aneurysm walls are associated with aneurysm rupture.","authors":"Nora Firtser, Eliisa Netti, Eliisa Kekäläinen, Satu Lehti, Petri T Kovanen, Mika Niemelä, Riikka Tulamo","doi":"10.1093/jnen/nlaf060","DOIUrl":"https://doi.org/10.1093/jnen/nlaf060","url":null,"abstract":"Chronic inflammation in saccular intracranial aneurysm (sIA) walls is associated with wall rupture. Previous studies have shown an association between macrophages and CD3+ T-lymphocytes with sIA wall degeneration and rupture but the roles of T-lymphocyte subtypes and B-lymphocytes are poorly understood. Here, cyclic multiplexed immunofluorescent staining was used to investigate the presence of T-lymphocytes helper CD4+ and cytotoxic CD8+ T-lymphocytes and CD20+ B-lymphocytes in 16 unruptured and 20 ruptured sIA walls. The sIA walls contained both CD4+ (n = 25/35) and CD8+ (n = 21/35) subtypes. There was a greater density of CD4+ T-lymphocytes (median 7, range 0-642 cells/mm2) vs CD8+ T-lymphocytes (median 1, range 0-30 cells/mm2). The density of CD4+ T-lymphocytes was associated with wall rupture, the presence of an intraluminal thrombus and numbers of vascular and lymphatic neovessels. Additionally, the densities of CD20+ B- and CD4+ T-lymphocytes were associated with atherosclerosis- and inflammation-related changes, such as the accumulation of apolipoprotein B-100 and serum amyloid A, and densities of CD68+ and CD163+ macrophages. These findings suggest that CD4+ T-lymphocytes play a role in sIA rupture, and that CD4+ T- and CD20+ B-lymphocytes contribute to sIA wall inflammation, particularly in the presence of atherosclerotic changes.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266445","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

Compound muscle action potential as an early functional in vivo measure of Sarm1 inhibition after sciatic nerve transection. 复合肌动作电位作为坐骨神经横断后Sarm1抑制的早期功能体内测量。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-06-06 DOI: 10.1093/jnen/nlaf066

Seong Kwon Hur, Rebecca R Leahey, Mitchell Geringer, Chang Hoon Cho, Hilda Hernandez-Barry, Jichu Pang, William S Sawyer, Miriam Baca, Marika Nespi, Raymond R Asuncion, ManKin Choy, James Maksymetz, Stephen T Vito, Jose Imperio, Kimberly Stark, Samantha A Green, Bryan K Chan, Luke Xie, Justin Ly, Alicia A Nugent, Jeffrey W Hofmann, Flora I Hinz, Martin Weber

{"title":"Compound muscle action potential as an early functional in vivo measure of Sarm1 inhibition after sciatic nerve transection.","authors":"Seong Kwon Hur, Rebecca R Leahey, Mitchell Geringer, Chang Hoon Cho, Hilda Hernandez-Barry, Jichu Pang, William S Sawyer, Miriam Baca, Marika Nespi, Raymond R Asuncion, ManKin Choy, James Maksymetz, Stephen T Vito, Jose Imperio, Kimberly Stark, Samantha A Green, Bryan K Chan, Luke Xie, Justin Ly, Alicia A Nugent, Jeffrey W Hofmann, Flora I Hinz, Martin Weber","doi":"10.1093/jnen/nlaf066","DOIUrl":"https://doi.org/10.1093/jnen/nlaf066","url":null,"abstract":"The NADase sterile alpha and TIR motif containing 1 (Sarm1) protein drives axon degeneration after injury. Loss or inhibition of Sarm1 structurally protects axons after sciatic nerve transection (SNT) in vivo but whether Sarm1 also drives functional loss after nerve injury is less clear. We established compound muscle action potential (CMAP) as a novel functional correlate of Sarm1 activation in a SNT mouse model and evaluated its relationship with biochemical and a novel Cellpose-based histological axon detection measure. CMAP amplitudes were elicited 8 h post-SNT but reached near-floor levels by 24 h. Decreases in CMAP amplitude are delayed in a gene dose-dependent manner in Sarm1 knockout mice or by pharmacological Sarm1 inhibition. Myelinated axon density, the NAD hydrolysis product cyclic adenosine diphosphate ribose (cADPR), and the axon degeneration plasma biomarker neurofilament light (NfL) were all altered in a Sarm1-dependent manner. In wild type mice, axon density and NfL were altered at time points after that of cADPR and functional loss, indicating that functional deficits preceded structural deficits. We conclude that functional and structural declines after injury are delayed by Sarm1 inhibition and that CMAP measures after SNT can serve as a novel, preclinical, functional, pharmacodynamic readout for Sarm1 inhibition.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234396","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

PAS+/PASD- intracytoplasmic glycogen is not specific for clear cell meningioma. PAS+/PASD-胞浆内糖原对透明细胞脑膜瘤无特异性。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-06-06 DOI: 10.1093/jnen/nlaf065

Merryl Terry, Gerald Reis, Melike Pekmezci, Joanna J Phillips, Andrew Bollen, Tarik Tihan, Arie Perry

引用次数: 0

Photobiomodulation therapy: Location-dependent effects on memory and recovery in male adult rats with spinal cord injury. 光生物调节疗法：位置依赖性对脊髓损伤雄性成年大鼠记忆和恢复的影响。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-05-30 DOI: 10.1093/jnen/nlaf051

Majid Kazemi, Ali Motamed Nezhad, Razieh Hajisoltan, Fatemeh Ramezani, Soroush Taherkhani, Fariborz Moayer, Faraz Moayer, Atousa Janzadeh, Ali Dadseresht, Reza Ahadi, Negin Mojarad, Mina Eftekharzadeh, Fazel Gorjipour

{"title":"Photobiomodulation therapy: Location-dependent effects on memory and recovery in male adult rats with spinal cord injury.","authors":"Majid Kazemi, Ali Motamed Nezhad, Razieh Hajisoltan, Fatemeh Ramezani, Soroush Taherkhani, Fariborz Moayer, Faraz Moayer, Atousa Janzadeh, Ali Dadseresht, Reza Ahadi, Negin Mojarad, Mina Eftekharzadeh, Fazel Gorjipour","doi":"10.1093/jnen/nlaf051","DOIUrl":"https://doi.org/10.1093/jnen/nlaf051","url":null,"abstract":"Spinal cord injuries (SCIs) can cause significant physical and emotional challenges for individuals as a result of inflammation and cell death. This study investigates the effectiveness of photobiomodulation therapy (PBMT) in reducing inflammation and memory impairment through the use of 3 specific treatment protocols. Forty male rats (180-200 g) were divided into 5 groups: Control; SCI model; and SCI with 3 different PBMT protocols. The rats underwent behavioral tests (Novel Object Recognition and Shuttle Box), histological examination (H&E and Nissl staining), and protein analysis (HDAC2, NF-kB [p65], IkB-α, and BDNF) using Western blot of medial prefrontal cortex (mPFC) and hippocampal tissues. PBMT effectively decreased NF-κB levels in the mFPC in all 3 PBMT protocols. The third PBMT3 protocol with the highest energy delivery, which included both the spinal cord and skull had the greatest impact on regulating the expression of this inflammatory factor. Behavioral assessments revealed that the PBMT3 protocol led to the most significant enhancement in cognition. The therapeutic effects of PBMT on memory are thought to be mediated by the enhancement of neurotrophic factors such as BDNF and the reduction of inflammatory mediators, which can impair hippocampal and mPFC function.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187205","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

A comparison of CDKN2A status in gliomas using different techniques: The loss of p16 as a surrogate marker. 不同技术在胶质瘤中CDKN2A状态的比较：p16作为替代标记物的缺失。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-05-30 DOI: 10.1093/jnen/nlaf062

Arnault Tauziède-Espariat, Audrey Rousseau, Laetitia Basset, Raphaël Saffroy, Ana Cavillon, Amélie Lusque, Lauren Hasty, Alice Métais, Yvan Nicaise, Emmanuelle Uro-Coste, Pascale Varlet

{"title":"A comparison of CDKN2A status in gliomas using different techniques: The loss of p16 as a surrogate marker.","authors":"Arnault Tauziède-Espariat, Audrey Rousseau, Laetitia Basset, Raphaël Saffroy, Ana Cavillon, Amélie Lusque, Lauren Hasty, Alice Métais, Yvan Nicaise, Emmanuelle Uro-Coste, Pascale Varlet","doi":"10.1093/jnen/nlaf062","DOIUrl":"https://doi.org/10.1093/jnen/nlaf062","url":null,"abstract":"The presence of a CDKN2A homozygous deletion (HD) plays an important role in the diagnostic approach for neuropathologists and the clinical prognostic stratification of several CNS tumors. CDKN2A is located on chromosome 9p21 next to CDKN2B and MTAP and encodes for the protein p16. Various molecular diagnostics are routinely used for assessing the deletion. In this context, we studied a cohort of 40 adult-type gliomas to analyze the concordance of three different molecular techniques, ie, FISH, NGS, and SNP array, for determining CDKN2A status and compared the results to p16 and MTAP immunostainings. The results showed that SNP array is the most reliable technique for the detection of CDKN2A HD and that p16 IHC constitutes a surrogate for the detection of biallelic inactivation of CDKN2A. p16 IHC was more accurate than MTAP IHC in detecting CDKN2A HD because a subset of CDKN2A HD gliomas did not present a deletion of the MTAP gene. IHC also allowed the detection of tumors with a hemizygous deletion of CDKN2A harboring a concomitant second molecular event on the remaining allele, ie, hypermethylation of CDKN2A promoter. We conclude that p16 immunostaining is an accurate biomarker for detecting CDKN2A HD.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208726","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

Merlin immunoreactivity fails to predict neurofibromatosis type 2 mutations in human meningiomas. Merlin免疫反应性不能预测人脑膜瘤中的2型神经纤维瘤病突变。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-05-30 DOI: 10.1093/jnen/nlaf058

Sofie Eline Tollefsen, Rahmina Meta, Ole Solheim, Patricia Mjønes, Ingfrid Vestrheim, Wenche Sjursen, Sverre Helge Torp

{"title":"Merlin immunoreactivity fails to predict neurofibromatosis type 2 mutations in human meningiomas.","authors":"Sofie Eline Tollefsen, Rahmina Meta, Ole Solheim, Patricia Mjønes, Ingfrid Vestrheim, Wenche Sjursen, Sverre Helge Torp","doi":"10.1093/jnen/nlaf058","DOIUrl":"https://doi.org/10.1093/jnen/nlaf058","url":null,"abstract":"Deletion in 22q and mutations in the neurofibromatosis type 2 (NF2) gene are frequent in sporadic meningiomas. The tumor suppressor protein merlin is encoded by NF2, and mutations may promote tumor development. NF2 status is increasingly important in meningioma diagnostics and we questioned whether merlin immunohistochemistry could be used as an accessible and affordable surrogate marker for prediction of NF2 mutations. Previous studies on merlin immunoreactivity have reported diverging results. We aimed to describe the immunohistochemical expression of merlin in a large series of meningiomas and relate these findings to clinicopathological features and NF2 status. Standardized immunohistochemistry was conducted on 172 meningiomas using three different merlin antibodies directed toward the N-terminal, C-terminal and phospho-merlin (ser 518). Twenty of the included cases had known NF2 status. All tumor specimens were immunoreactive for the three merlin antibodies. The immunoreactivity of phosphorylated merlin was higher in meningothelial tumors. There were no other significant associations between merlin immunoreactivity and NF2 status, WHO grade, tumor subtype, tumor location or gender. These results indicate that merlin immunoreactivity does not seem to be predictive of NF2 mutation, as merlin was abundantly expressed by all included tumors and independently of NF2 status.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187204","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

Shift of DNA methylation class may occur on recurrence of pleomorphic xanthoastrocytoma. 多形性黄色星形细胞瘤复发时可能发生DNA甲基化类别的转移。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-05-27 DOI: 10.1093/jnen/nlaf061

Gonzalo Hernandez Gamero, Evelina Miele, Andrea Mafficini, Lucrezia Ghione, Sara Patrizi, Lucia Pedace, Serena Ammendola, Valeria Barresi

引用次数: 0

Long non-coding RNAs plasmacytoma variant translocation 1 regulates bone marrow mesenchymal stem cell transplantation to promote the repair of spinal cord injury. 长链非编码rna浆细胞瘤变异易位1调控骨髓间充质干细胞移植促进脊髓损伤修复。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-05-26 DOI: 10.1093/jnen/nlaf052

Lei Gao, Peng Li, Ruize Yang, Wenchao Bi, Fanbo Meng, Lei Xia

{"title":"Long non-coding RNAs plasmacytoma variant translocation 1 regulates bone marrow mesenchymal stem cell transplantation to promote the repair of spinal cord injury.","authors":"Lei Gao, Peng Li, Ruize Yang, Wenchao Bi, Fanbo Meng, Lei Xia","doi":"10.1093/jnen/nlaf052","DOIUrl":"https://doi.org/10.1093/jnen/nlaf052","url":null,"abstract":"This study investigated the therapeutic potential of long non-coding RNAs plasmacytoma variant translocation 1 (lncRNA PVT1) in regulating the function of bone marrow mesenchymal stem cells (BMSCs) following experimental spinal cord injury (SCI). Rat BMSCs were isolated and characterized. Loss-of and gain-of-function experiments were performed to assess the effects of lncRNA PVT1 on BMSCs and Schwann cells (SCs). Fusion PCR mutation, dual-luciferase reporter, and RNA immunoprecipitation assays were employed to explore the binding region between lncRNA PVT1 and polypyrimidine tract binding protein 1 (PTBP1). LncRNA PVT1 increased the proliferation, migration, and apoptosis of BMSCs; lncRNA PVT1 knockdown had the opposite effects. LncRNA PVT1 inhibited PTBP1 expression. The promoting effect of lncRNA PVT1 on the proliferation and migration of BMSCs was suppressed by overexpression of PTBP1. LncRNA PVT1 also induced SC-like differentiation of BMSCs. LncRNA PVT1-modified BMSCs promoted the proliferation and migration of SCs and upregulated levels of neurotrophic factors and SC biomarkers. Transplantation of lncRNA PVT1-modified BMSCs also improved functional recovery of rats with SCI. Altogether, lncRNA PVT1 promoted the proliferation, migration, and differentiation of BMSCs by inhibiting PTBP1. LncRNA PVT1-modified BMSCs also influenced the function of SCs and promoted recovery in rats following SCI.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142904","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

Insights into holoprosencephaly using multimodal high-resolution imaging and 3D histology. 利用多模态高分辨率成像和3D组织学研究前脑畸形。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-05-24 DOI: 10.1093/jnen/nlaf057

Jaikishan Jayakumar, Jivitha Jyothi Ramesh, Rebecca D Folkerth, S Latha, Harish Kumar, S Suresh, Chitra Srinivasan, Jayaraman Kumutha, Richa Verma, Mohanasankar Sivaprakasam

{"title":"Insights into holoprosencephaly using multimodal high-resolution imaging and 3D histology.","authors":"Jaikishan Jayakumar, Jivitha Jyothi Ramesh, Rebecca D Folkerth, S Latha, Harish Kumar, S Suresh, Chitra Srinivasan, Jayaraman Kumutha, Richa Verma, Mohanasankar Sivaprakasam","doi":"10.1093/jnen/nlaf057","DOIUrl":"https://doi.org/10.1093/jnen/nlaf057","url":null,"abstract":"Holoprosencephaly (HPE) is a well-described forebrain patterning disorder in mid-late gestation fetuses and infants. Here, we used a novel, whole-brain multimodal approach (ultrasonography, magnetic resonance imaging, and histology with 3-dimensional [3D] reconstructions with cell mapping) in earlier-gestation specimens than previously reported. In one 13- and two 22-gestational week fetuses and age-matched controls, we elucidated heretofore underappreciated HPE findings of (1) abnormal clustering of immature (doublecortin-immunoreactive) cells in the midline and paramedian forebrain, (2) linear arrays of cells in the intermediate zone of the cerebral mantle (reminiscent of subcortical band heterotopia, but possibly transient), (3) \"reactive\"-appearing glial fibrillary acidic protein-immunoreactive cortical cells, and (4) apparent \"midline fusion\" of rostral ganglionic eminences. We observed disorganization of orbitofrontal cortices and midline structures, rostral subarachnoid (marginal zone) heterotopia, and lateral displacement of the hippocampal formations utilizing multiscale multimodal 3D analytics. These findings shed light on the temporal evolution of HPE at earlier gestational ages. Moreover, this approach is scalable to include the wide range of phenotypes of HPE and is applicable to other neurologic disorders, including developmental as well as adult vascular, infectious, neoplastic, and degenerative conditions for which spatial analyses permit a fuller understanding of their pathologic spectrum.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136174","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

Biopsy-proven granulomatous neuromyopathy in a case of Blau syndrome. Blau综合征肉芽肿性神经肌病1例活检证实。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-05-23 DOI: 10.1093/jnen/nlaf056

Nadeem Toodayan, Joseph Stockwell, Judith Spies, Joanne Sy, Rajiv Wijesinghe, Benjamin Nham

引用次数: 0