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

Characterization of Chitinase 3-like protein 1 spatiotemporal distribution in human post-traumatic brain contusions and other neuropathological scenarios. 几丁质酶3样蛋白1在人创伤后脑挫伤及其他神经病理情景中的时空分布特征

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-01 DOI: 10.1093/jnen/nlaf002

Cristina Sánchez Carabias, Victoria Cunha Alves, Aurelio Hernández Laín, Alfonso Lagares

{"title":"Characterization of Chitinase 3-like protein 1 spatiotemporal distribution in human post-traumatic brain contusions and other neuropathological scenarios.","authors":"Cristina Sánchez Carabias, Victoria Cunha Alves, Aurelio Hernández Laín, Alfonso Lagares","doi":"10.1093/jnen/nlaf002","DOIUrl":"10.1093/jnen/nlaf002","url":null,"abstract":"Chitinase 3-like protein 1 (CHI3L1) is emerging as a promising biomarker for assessing intracranial lesion burden and predicting prognosis in traumatic brain injury (TBI) patients. Following experimental TBI, Chi3l1 transcripts were detected in reactive astrocytes located within the pericontusional cortex. However, the cellular sources of CHI3L1 in response to hemorrhagic contusions in human brain remain unidentified. Hence, we examined a comprehensive collection of histologically defined acute and subacute human cerebral contusions with various surgical intervals using immunohistochemistry, validated through double immunofluorescence for markers such as GFAP, NeuN, MBP, and Iba-1, along with Fluoro-Jade C histofluorescence staining. CHI3L1 was found at meningeal interfaces, showing significant thickening of subpial glial plate. Paradoxically, CHI3L1-positive astrocytes were identified in neuroanatomical locations distant from hemorrhagic foci, where numerous eosinophilic ischemic neurons also exhibited CHI3L1 immunoreactivity. CHI3L1 immunostaining extended into white matter tracts and highlighted various phagocytic or activated microglia forms after delayed surgical decompressions. Given these findings, we advise against using CHI3L1 as a reactive astrogliosis marker due to its expression in multiple cell types, including astrocytes, neurons, oligodendrocytes, ependymocytes, leptomeningeal cells, microglia, and blood vessels. This non-selective response underscores the potential for CHI3L1 elevation patterns in biofluids to reflect the overall lesion burden extent.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"305-328"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007227","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

Intramural hematomas and astrocytic infiltration precede perivascular inflammation in a rat model of repetitive low-level blast injury. 在大鼠重复性低水平爆炸损伤模型中，壁内血肿和星形细胞浸润先于血管周围炎症。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-01 DOI: 10.1093/jnen/nlaf003

Miguel A Gama Sosa, Rita De Gasperi, Rachel H Lind, Dylan Pryor, Danielle C Vargas, Georgina S Perez Garcia, Gissel M Perez, Rania Abutarboush, Usmah Kawoos, Allison Sowa, Carolyn W Zhu, William G M Janssen, Patrick R Hof, Stephen T Ahlers, Gregory A Elder

{"title":"Intramural hematomas and astrocytic infiltration precede perivascular inflammation in a rat model of repetitive low-level blast injury.","authors":"Miguel A Gama Sosa, Rita De Gasperi, Rachel H Lind, Dylan Pryor, Danielle C Vargas, Georgina S Perez Garcia, Gissel M Perez, Rania Abutarboush, Usmah Kawoos, Allison Sowa, Carolyn W Zhu, William G M Janssen, Patrick R Hof, Stephen T Ahlers, Gregory A Elder","doi":"10.1093/jnen/nlaf003","DOIUrl":"10.1093/jnen/nlaf003","url":null,"abstract":"In modern war theaters, exposures to blast overpressures are one of the most common causes of brain injury. These pervasive events result in acute and chronic cerebrovascular degenerative processes. Using a rat model of blast-induced mild traumatic brain injury, we identified intramural periarterial hematomas as early primary acute lesions induced by blast exposures. These lesions resulted in intravascular cell death, cell layer reorganization, and plasma leakage into the intraperiarterial basal membranes that constitute the intraperiarterial drainage system (IPAD). Plasma metalloproteases, including MMP-9, in the IPAD basal membranes may degrade extracellular matrix components compromising normal cerebral interstitial fluid drainage, arterial structure and function leading to chronic vascular degenerative processes. Related subacute effects of blast exposure included increased MMP-9 expression in perivascular reactive astrocytes and the extension of astrocytic processes through the layers of affected vessels. These results, in combination with normal levels of proinflammatory cytokines and the absence of proinflammatory MHC II-expressing microglia, suggest an astrocytic role in the clearing of intravascular hematomas and provide further mechanistic evidence that blast-induced vascular degenerative processes may precede the onset of neurovascular inflammation.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"337-352"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046847","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

Meningiomas in Rubinstein-Taybi syndrome: A case report and comprehensive review. 鲁宾斯坦-泰比综合征中的脑膜瘤：病例报告和综合综述。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-01 DOI: 10.1093/jnen/nlae135

Andrea Chen, Shannon Louise Hart, Melissa Lannon, Cynthia Hawkins, Kesava K V Reddy, Jian-Qiang Lu

{"title":"Meningiomas in Rubinstein-Taybi syndrome: A case report and comprehensive review.","authors":"Andrea Chen, Shannon Louise Hart, Melissa Lannon, Cynthia Hawkins, Kesava K V Reddy, Jian-Qiang Lu","doi":"10.1093/jnen/nlae135","DOIUrl":"10.1093/jnen/nlae135","url":null,"abstract":"Rubinstein-Taybi syndrome (RTS) is a congenital disorder with characteristic clinical manifestations. In the vast majority of cases, it is caused by mutations of the gene encoding the transcriptional co-activator cAMP-response element binding protein (CBP)-binding protein (CREBBP). It has been thought to be a tumor predisposition syndrome as RTS patients have an increased risk of developing tumors including meningiomas. However, RTS-associated meningiomas are rarely reported. We report a unique RTS-associated meningioma in which an oncogenic CREBBP mutation is identified. We also comprehensively review the reported RTS-associated meningiomas, from epidemiology and pathogenesis to clinicopathological characteristics and treatment. All RTS patients with meningiomas are female and have the exclusive mutations of CREBBP. In population-based studies RTS-associated meningiomas seem to develop at younger ages. Their pathogenesis may be driven by the CREBBP/CBP alterations resulting in aberrant signal transduction in the CBP-mediated signaling pathways. Meningiomas in RTS patients have common clinicopathological characteristics including comorbidity with other tumors, radiologically intra-osseous growth, and uncommon histopathology such as ossifying and secretory features. Given the genetic nature and rarity of RTS-associated meningiomas, further investigation of their characteristics may define molecular targets for improved therapeutic options for RTS patients.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"329-336"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909854","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

α-Synuclein distribution in olfactory mucosa and skin nerves in Parkinson disease associated with an EIF4G1 gene mutation. α-突触核蛋白在帕金森病嗅觉黏膜和皮肤神经中的分布与EIF4G1基因突变相关

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-01 DOI: 10.1093/jnen/nlaf001

Arianna Braccia, Antonio Emanuele Elia, Grazia Devigili, Raffaella Lombardi, Alessia Luppino, Samanta Mazzetti, Celeste Panteghini, Isabel Colangelo, Marta Suerz, Sara Maria Portaleone, Anna Maria Perilli, Chiara Maria Giulia De Luca, Arianna Ciullini, Ilaria Linda Dellarole, Roberta Telese, Barbara Garavaglia, Fabio Moda, Roberto Eleopra

{"title":"α-Synuclein distribution in olfactory mucosa and skin nerves in Parkinson disease associated with an EIF4G1 gene mutation.","authors":"Arianna Braccia, Antonio Emanuele Elia, Grazia Devigili, Raffaella Lombardi, Alessia Luppino, Samanta Mazzetti, Celeste Panteghini, Isabel Colangelo, Marta Suerz, Sara Maria Portaleone, Anna Maria Perilli, Chiara Maria Giulia De Luca, Arianna Ciullini, Ilaria Linda Dellarole, Roberta Telese, Barbara Garavaglia, Fabio Moda, Roberto Eleopra","doi":"10.1093/jnen/nlaf001","DOIUrl":"10.1093/jnen/nlaf001","url":null,"abstract":"The EIF4G1 gene has been considered an autosomal dominant cause of Parkinson disease (PD), even if its role is still debated. The objective of this study was to describe the phenotype and α-synuclein distribution in peripheral tissues in 2 related PD patients (mother and daughter), who are carriers of the same variant in exon 10 of EIF4G1 (c.1216G>A, p.Gly406Arg). We used the Burghart Sniffin Sticks test for olfactory function. α-Synuclein distribution in the olfactory mucosa and skin samples was analyzed using RT-QuIC, double immunofluorescence, and immunohistochemical staining. Both patients presented with a mild motor syndrome associated with hyposmia as prominent traits; pathological α-synuclein deposits were found in the olfactory mucosa but not in the skin. The phenotype and the findings in peripheral tissues suggest that PARK18 could manifest as a \"benign\" form of PD associated with hyposmia, with a slow progression and sparse α-synuclein accumulation in the peripheral nervous system.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"286-292"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047021","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

Cytoplasmic expression of trans-active response DNA-binding protein-43 in aged mice display hippocampal sclerosis-like degeneration and neuronal loss with reduced lifespan. 衰老小鼠细胞质表达的反式反应dna结合蛋白43表现出海马硬化样变性和神经元丧失，寿命缩短。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-01 DOI: 10.1093/jnen/nlae137

Ashley J Anderson, Matthew B Dopler, Sanaz Arezoumandan, Damian Osei-Kankam, Stephani A Davis, Kaouther Ajroud, Jaclyn Lilek, Eva Bambakadis, Rachel Shapiro, Margaret E Flanagan, Nigel J Cairns, Michael A Gitcho

{"title":"Cytoplasmic expression of trans-active response DNA-binding protein-43 in aged mice display hippocampal sclerosis-like degeneration and neuronal loss with reduced lifespan.","authors":"Ashley J Anderson, Matthew B Dopler, Sanaz Arezoumandan, Damian Osei-Kankam, Stephani A Davis, Kaouther Ajroud, Jaclyn Lilek, Eva Bambakadis, Rachel Shapiro, Margaret E Flanagan, Nigel J Cairns, Michael A Gitcho","doi":"10.1093/jnen/nlae137","DOIUrl":"10.1093/jnen/nlae137","url":null,"abstract":"Trans-active response DNA-binding protein-43 (TDP-43) is the major pathological protein in motor neuron disease and TDP-43 pathology has been described in the brains of up to 50% of patients with Alzheimer disease (AD). Hippocampal sclerosis of aging (HS-A), an age-related neuropathology characterized by severe neuronal loss and gliosis in CA1 and/or subiculum, is found in ∼80% of cases that are positive for phosphorylated TDP-43. HS-A is seen as a co-pathology in cases with AD, limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC), and frontotemporal degeneration. To understand the pathogenetic relationships between HS-A and LATE-NC, mice that selectively express human TDP-43 and TDP-43 with a defective nuclear localization signal (ΔNLS) in the hippocampus, alone or in an APP/PSEN1 background, were evaluated using histology, HALO software's object recognition algorithms, and protein expression assays. Twenty-four-month-old mice expressing cytosolic TDP-43 displayed marked neuronal loss and atrophy in the hippocampus, decreased β-amyloid plaque deposition and modulation of microglia and intermediate filament activation. TDP-43ΔNLS-expressing mice survived to only ∼24 months of age whether or not they had an APP/PSEN1 background. This HS-A-like model may provide insights into the pathogenesis of neurodegeneration seen in HS-A and in other TDP-43 proteinopathies.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"293-304"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046844","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

Aberrant accumulation of phosphorylated BRCA1 in brainstem-type and cortical-type Lewy bodies in Lewy body disease. 路易体病中脑干型和皮质型路易体中磷酸化BRCA1的异常积累

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-01 DOI: 10.1093/jnen/nlaf004

Masataka Nakamura, Aya Murakami, Dennis W Dickson, Yusuke Yakushiji

{"title":"Aberrant accumulation of phosphorylated BRCA1 in brainstem-type and cortical-type Lewy bodies in Lewy body disease.","authors":"Masataka Nakamura, Aya Murakami, Dennis W Dickson, Yusuke Yakushiji","doi":"10.1093/jnen/nlaf004","DOIUrl":"10.1093/jnen/nlaf004","url":null,"abstract":"BRCA1 plays important roles in several biological events during the DNA damage response (DDR). We aimed to determine whether cytoplasmic accumulation of BRCA1 or its phosphorylated form, pBRCA1, is specific to cytoplasmic inclusions in tauopathies, or if it also occurs in α-synuclein-positive inclusions in Lewy body disease (LBD). Using brain tissue from pure LBD, LBD with Alzheimer disease (AD) co-pathology (LBD-AD), and control cases, the immunohistochemical distributions of BRCA1, pBRCA1, its binding partner BARD1, and 53BP1 were examined. The results showed that pBRCA1 (Ser1423) and BARD1 accumulated in brainstem-type Lewy bodies (LBs), whereas only pBRCA1 (Ser1423) was present in cortical-type LBs. There was no significant difference in the frequency of pBRCA1 (Ser1423)-positive LBs between the pure LBD and LBD-AD cases. pBRCA1 (Ser1423) was minimally detected in neuronal nuclei in controls and was absent in neuronal nuclei in LBD cases. In control and LBD cases, 53BP1-immunoreactive deposits were present in the neuronal nuclei. Thus, DDR dysfunction due to cytoplasmic sequestration of pBRCA1 (Ser1423) may play a role in LBD pathogenesis. Additionally, the selective accumulation of BARD1 in brainstem-type LBs, but not cortical-type LBs, points to distinct mechanisms in the formation of these inclusion types, offering further insights into LBD pathology.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"276-285"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189702","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

Star-shaped TDP-43 inclusions in the oldest-old. 在最古老的植物中存在星形 TDP-43 包涵体。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-01 DOI: 10.1093/jnen/nlae116

Erin E Connolly, John F Ervin, Brenda L Plassman, Kathleen A Welsh-Bohmer, Shih-Hsiu J Wang

引用次数: 0

Therapeutic potential and challenges of mesenchymal stem cells in neurological disorders: A concise analysis. 间充质干细胞治疗神经系统疾病的潜力和挑战：简明分析。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-03-27 DOI: 10.1093/jnen/nlaf021

Enas H Bani Issa, Enas M Alghazo, Raghad Gharaibeh, Noor B Momani, Dana Z Taha, Renad J Jaradat, Ayman Alzu'bi, Fatimah A Almahasneh, Ejlal Abu-El-Rub, Raed M Al-Zoubi

{"title":"Therapeutic potential and challenges of mesenchymal stem cells in neurological disorders: A concise analysis.","authors":"Enas H Bani Issa, Enas M Alghazo, Raghad Gharaibeh, Noor B Momani, Dana Z Taha, Renad J Jaradat, Ayman Alzu'bi, Fatimah A Almahasneh, Ejlal Abu-El-Rub, Raed M Al-Zoubi","doi":"10.1093/jnen/nlaf021","DOIUrl":"https://doi.org/10.1093/jnen/nlaf021","url":null,"abstract":"Neurological diseases comprise a wide array of conditions affecting both the central and peripheral nervous systems. Neurodegenerative diseases encompass a group of debilitating and often fatal neurological disorders for which effective treatments are currently lacking. Stem cells are recognized for their remarkable capacity for proliferation, multilineage differentiation, and self-renewal. The transplantation of stem cells represents a significant advancement in therapeutic strategies for neurological disorders, with applications in both preclinical and clinical settings. Mesenchymal stem cells (MSCs), in particular, have garnered substantial interest due to their unique properties, making them a highly sought-after source of therapeutic cells. Although the efficacy of MSCs in treating neurological disorders is well documented, further research is needed to elucidate the underlying mechanisms and to assess their in vivo applications more comprehensively. This article summarizes current research on the use of MSCs in the treatment of various neurological disorders, including Parkinson disease, stroke, multiple sclerosis, and Alzheimer disease.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730508","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

Systemic anaplastic lymphoma kinase-negative anaplastic large cell lymphoma with prominent meningeal involvement: A case report. 全身性无细胞淋巴瘤激酶阴性无细胞大细胞淋巴瘤，脑膜明显受累：病例报告。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-03-27 DOI: 10.1093/jnen/nlaf023

Yingxue Yang, Ziyan Zhu, Yajie Wang, Yueshan Piao, Hua Lin

引用次数: 0

Expanding the spectrum of TERT promoter mutations in CNS tumors: A case series of non-canonical mutations. 扩大中枢神经系统肿瘤中TERT启动子突变的范围：一系列非典型突变的病例。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-03-19 DOI: 10.1093/jnen/nlaf022

David J Cook, Jorge A Trejo-Lopez, Beth A Pitel, Neiladri Saha, Tejaswi Koganti, Jayson Hardcastle, Stephanie Smoley, Matthew Isaacson, Mallika Gandham, Gopinath Sivasankaran, Surendra Dasari, Kar-Ming Fung, Suzanne Z Powell, Darshan Trivedi, Zied Abdullaev, Kenneth Aldape, Martha Quezado, Drew Pratt, Patrick Joseph Cimino, Mark A Edgar, Rachael A Vaubel, Aditya Raghunathan, Caterina Giannini, Robert B Jenkins, Cristiane M Ida

引用次数: 0