Journal of Neuropathology and Experimental Neurology最新文献_第3页

Different cortical and subcortical astroglial responsiveness in rats with acute liver failure. 急性肝衰竭大鼠皮层和皮层下星形胶质细胞反应性的差异。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-05-01 DOI: 10.1093/jnen/nlaf020

Nahla Ouard, Assmaâ Tali, Themoi Demsou Souhoudji, Rajâa Jebbouj, Ihssane El-Bouchikhi, Christopher F Rose, Samir Ahboucha

{"title":"Different cortical and subcortical astroglial responsiveness in rats with acute liver failure.","authors":"Nahla Ouard, Assmaâ Tali, Themoi Demsou Souhoudji, Rajâa Jebbouj, Ihssane El-Bouchikhi, Christopher F Rose, Samir Ahboucha","doi":"10.1093/jnen/nlaf020","DOIUrl":"10.1093/jnen/nlaf020","url":null,"abstract":"Hepatic encephalopathy (HE) is a neuropsychiatric complication of liver failure. Previous studies described astroglia alterations in HE, but regional changes have not been well investigated. This study addresses regional astroglial response by exploring glial fibrillary acidic protein (GFAP) immunoreactivity in cortical structures including somatosensory (S1Tr and S1BF), piriform (Pir), and perirhinal (PRh) cortices, and subcortical regions including corpus callosum (CC), ventromedial thalamus (VMT), mammillothalamic tract (MTT), and dorsomedial hypothalamic nucleus (DHN) in rats with acute liver failure (ALF) sacrificed at coma stage. Our data showed decreased numbers of astrocytes in S1Tr, Pir, and CC in ALF rats. GFAP-immunoreactive cells were increased within other regions including PRh, VMT, MTT, and DHN. Cell morphometric analysis showed significant increase in GFAP-immunoreactive astrocyte processes and cell bodies in cortical and subcortical regions but not in CC and DHN. However, astrocyte perimeters were increased, particularly in S1Tr and VMT. Our study demonstrates regional specificity including (1) regions with astrocyte activation associated with an increase of GFAP-immunostaining and astrocyte cell counts, together with (2) unaltered GFAP components, and (3) regions characterized by presumably inactive astrocyte with a reduced GFAP-immunostaining. These findings may reflect either different regional alterations in HE, or stages of an alteration progressing differently in different regions.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"412-422"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772546","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

Authors' response to Dr Miller's letter: "Machaalani et al. concerning dentate gyrus dysplasia". 作者对米勒博士来信的回应：“Machaalani等人关于齿状回发育不良”。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-05-01 DOI: 10.1093/jnen/nlaf012

Rita Machaalani, Michael Rodriguez

引用次数: 0

Presenilin 1 M139I mutation regulates the microRNA-34a-mediated neurogenic locus notch homolog protein 1 signaling pathway in an early-onset Alzheimer disease cell model. 早老素1m139i突变调控早发性阿尔茨海默病细胞模型中microrna -34a介导的神经源性基因座缺口同源蛋白1信号通路

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-26 DOI: 10.1093/jnen/nlaf044

Xuechun Sun, Lijun Dai, Xin Yuan, Lufeng Cheng, Jing Wang, Ye Tian, Lingyan Zhou

{"title":"Presenilin 1 M139I mutation regulates the microRNA-34a-mediated neurogenic locus notch homolog protein 1 signaling pathway in an early-onset Alzheimer disease cell model.","authors":"Xuechun Sun, Lijun Dai, Xin Yuan, Lufeng Cheng, Jing Wang, Ye Tian, Lingyan Zhou","doi":"10.1093/jnen/nlaf044","DOIUrl":"https://doi.org/10.1093/jnen/nlaf044","url":null,"abstract":"Presenilin 1 (PSEN1) mutations are the leading cause of early-onset Alzheimer disease (EOAD). A recent study found that the PSEN1 M139I mutation is associated with EOAD. In this study, we examined the impact of the PSEN1 M139I mutation in an EOAD in vitro model. Our findings reveal that the PSEN1 M139I mutation leads to increased levels of Aβ42/40, Hairy and Enhancer of Split-1 (Hes1), neurogenic locus notch homolog intracellular domain, and microRNA-34a, accompanied by a decrease in the level of neurogenic locus notch homolog protein 1 (NOTCH-1). Computational predictions indicate that NOTCH-1 is a direct target of microRNA-34a. Transfection of microRNA-34a mimics into PSEN1 M139I mutant SH-SY5Y cells increased the ratio of Aβ42/40 and induced Hes1, cysteine-aspartic acid protease 3 (Caspase-3), and apoptosis while reducing the NOTCH-1 expression and inhibiting cell proliferation. Conversely, downregulating microRNA-34a expression by transfecting microRNA-34a inhibitors mitigated these effects, thereby restoring NOTCH-1 production and cell proliferation and reversing the increases in Aβ42/40 ratio, Hes1, Caspase-3, and apoptosis induced by the PSEN1 M139I mutation. In summary, the PSEN1 M139I mutation identified in EOAD may influence amyloid-β (Aβ) production and apoptosis by regulating the microRNA-34a-mediated NOTCH-1 signaling pathway.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064015","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

EGFR transcript variants: Potential diagnostic biomarker for glioblastoma, IDH-wildtype? EGFR转录变体：胶质母细胞瘤的潜在诊断生物标志物，idh野生型？

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-25 DOI: 10.1093/jnen/nlaf041

David J Cook, Paul A Decker, Jayson J Hardcastle, Tom M Kollmeyer, Stephanie A Smoley, Matthew D Isaacson, Mallika Gandham, Surendra Dasari, Zied Abdullaev, Kenneth Aldape, Martha Quezado, Patrick J Cimino, Drew W Pratt, Caterina Giannini, Aivi Nguyen, Aditya Raghunathan, Jorge A Trejo-Lopez, Rachael A Vaubel, M Adelita Vizcaino, Cinthya J Zepeda Mendoza, Hussam Al Kateb, Robert B Jenkins, Cristiane M Ida

引用次数: 0

Reliability and modeling of digital histological measurements in Alzheimer's disease neuropathologic change and Lewy body disease. 阿尔茨海默病、神经病理改变和路易体病的数字化组织学测量的可靠性和建模。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-24 DOI: 10.1093/jnen/nlaf047

Yongya Kim, Thea Andreasson, Namitha Vishupad, Avani Benegal, Donald Pizzo, Lawrence Hansen, Annie Hiniker, David Coughlin

{"title":"Reliability and modeling of digital histological measurements in Alzheimer's disease neuropathologic change and Lewy body disease.","authors":"Yongya Kim, Thea Andreasson, Namitha Vishupad, Avani Benegal, Donald Pizzo, Lawrence Hansen, Annie Hiniker, David Coughlin","doi":"10.1093/jnen/nlaf047","DOIUrl":"https://doi.org/10.1093/jnen/nlaf047","url":null,"abstract":"Digital histology offers a more objective, continuous definition of neuropathological severity than traditional staging systems, but its reliability remains underexplored. We calculated regional percentage areas occupied by phosphorylated tau (p-Tau, AT8), amyloid-β (Aβ, NAB228), and phosphorylated α-synuclein (p-αSyn, 81A) pathology in 24 autopsied cases with varying degrees of Alzheimer disease neuropathological change and Lewy body disease (LBD) using manual and automated immunostaining methods to investigate variability across protocols. We then compared natural log-transformed percent area occupied values (ln%AO) to blinded ordinal severity scores, Braak stages, Thal phases, and McKeith LBD stages. p-Tau ln%AO from methodologically similar runs had the highest correlations (R2 = 0.91-0.95, β = 0.95-0.97 for manual and automated methods, respectively); p-αSyn ln%AO from disparate immunostaining methods had the lowest (R2 = 0.16-0.34 β = 0.40-0.59). p-Tau and Aβ ln%AO increased regionally with higher Braak and Thal stages (p-Tau: z = 2.06 P = .04. Aβ: z = 3.70 P < .001). Regional p-αSyn ln%AO increased from limbic to neocortical stages (z = 5.86 P < .001); amygdala-predominant type LBD cases peaked in the amygdala and dropped in other limbic regions. These findings show the potential to quantify differences in p-Tau, Aβ, and p-αSyn pathologies using digital histological methods in single-center studies.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018852","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

The paradoxical relationship of sensorimotor deficit and lesion volume in acute ischemic stroke. 急性缺血性脑卒中感觉运动障碍与病变体积的矛盾关系。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-24 DOI: 10.1093/jnen/nlaf046

Réka Tóth, Nikoletta Szabó, Anna Törteli, Noémi Kovács, Ildikó Horváth, Krisztián Szigeti, Domokos Máthé, Tamás Zs Kincses, Ákos Menyhárt, Eszter Farkas

{"title":"The paradoxical relationship of sensorimotor deficit and lesion volume in acute ischemic stroke.","authors":"Réka Tóth, Nikoletta Szabó, Anna Törteli, Noémi Kovács, Ildikó Horváth, Krisztián Szigeti, Domokos Máthé, Tamás Zs Kincses, Ákos Menyhárt, Eszter Farkas","doi":"10.1093/jnen/nlaf046","DOIUrl":"https://doi.org/10.1093/jnen/nlaf046","url":null,"abstract":"Understanding the relationship between the degree of neurological deficit and lesion volume is key to predicting outcomes in patients with acute ischemic stroke (AIS). Over the past 40 years, AIS research has relied on a perceived linear relationship between lesion volumes and neurological deficit. Here, we found that these variables do not show a relationship in a mouse model of AIS. Acute ischemic stroke was induced by transient (60 minutes) intraluminal microfilament occlusion of the middle cerebral artery in 15 male isoflurane (0.8%-1%)-anesthetized mice. Acute ischemic stroke-induced sensorimotor deficits were assessed daily for 72 hours using the Garcia Neuroscore Scale (GNS). Lesion size was estimated 72 hours after AIS using a rodent MRI system. Lesion sizes ranged from 17 to 130 mm3. In 3/15 mice (atypical cases: lesion <30 mm3 and GNS <11), small infarcts (14.6 ± 6.2 vs 51.7 ± 19.9 mm3, atypical vs typical) were associated with low GNS values at 72 hours (9 ± 2 vs 11 ± 2 pts; atypical vs typical). Consequently, we found no relationship between lesion size and GNS in this AIS model (R = 0.058). These results suggest that lesion size is not a reliable predictor of neurological outcome in AIS models.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970672","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

SSTR2 expression in neoplastic and normal anterior pituitary is impacted by age, sex, and hormonal status. SSTR2在肿瘤和正常垂体前叶中的表达受年龄、性别和激素状况的影响。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-22 DOI: 10.1093/jnen/nlaf034

Benjamin Liechty, Sean Kim, Georgiana Dobri, Theodore H Schwartz, Jana Ivanidze, David Pisapia

{"title":"SSTR2 expression in neoplastic and normal anterior pituitary is impacted by age, sex, and hormonal status.","authors":"Benjamin Liechty, Sean Kim, Georgiana Dobri, Theodore H Schwartz, Jana Ivanidze, David Pisapia","doi":"10.1093/jnen/nlaf034","DOIUrl":"https://doi.org/10.1093/jnen/nlaf034","url":null,"abstract":"Pituitary neuroendocrine tumors (PitNETs) are among the most common tumors encountered in neurooncology. While the majority of PitNETs demonstrate indolent behavior, a subset of tumors demonstrates aggressive behavior, including invasion into surrounding structures. As traditional imaging has limited capacity to distinguish tumor from post-operative changes, better methods of tumor delineation are needed to guide management. Somatotroph adenomas are known to express high levels of SSTR2, and SSTR2-targeting PET imaging has shown clinical utility in the management of neuroendocrine tumors and meningiomas. In this retrospective study of archival PitNETs (n = 271) and autopsy controls (AC) (n = 20), we show that although significant differences in SSTR2 immunostaining are appreciable between adenoma subtypes and ACs, high-staining cases are encountered in all subtypes. In ACs, females demonstrated significantly stronger SSTR2 staining than males. Weak age-related trends towards increasing labelling in females and decreasing labelling in males were noted but these did not reach statistical significance. Decreasing age-related trends were seen in gonadotrophs in both sexes; this was statistically significant in females. Our findings suggest that SSTR2-targeting imaging modalities may assist clinical management of a subset of PitNETs and that these results may need to be interpreted with consideration of patient age and sex.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024236","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

Evaluation of 6 monoclonal antibodies against Ser129-phosphorylated α-synuclein: Critical role of proteinase K antigen retrieval and superior sensitivity of the D1R1R clone in human skin biopsies. 6种抗ser129磷酸化α-突触核蛋白单克隆抗体的评价：蛋白酶K抗原检索的关键作用和D1R1R克隆在人皮肤活检中的优越敏感性

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-22 DOI: 10.1093/jnen/nlaf036

Cecilia Delprete, Alex Incensi, Alessandro Furia, Riccardo Bari, Rocco Liguori, Vincenzo Donadio

{"title":"Evaluation of 6 monoclonal antibodies against Ser129-phosphorylated α-synuclein: Critical role of proteinase K antigen retrieval and superior sensitivity of the D1R1R clone in human skin biopsies.","authors":"Cecilia Delprete, Alex Incensi, Alessandro Furia, Riccardo Bari, Rocco Liguori, Vincenzo Donadio","doi":"10.1093/jnen/nlaf036","DOIUrl":"https://doi.org/10.1093/jnen/nlaf036","url":null,"abstract":"α-Synuclein is an essential component of synucleinopathies including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy (MSA). Misfolded-α-synuclein inclusions that contain high levels of Serine-129 phosphorylated (pS129-α-syn) are key diagnostic markers. Skin biopsies are a promising peripheral tissue for in vivo detection of aggregates using immunofluorescence staining. Several primary antibodies target pS129-α-syn but their diagnostic reliability remains uncertain. Common practice relies on clones EP1536Y and 81A without antigen retrieval; however, recent findings have underscored the need to validate additional methodologies and alternative clones. We compared the diagnostic accuracy of the standard protocol, alongside formic acid and proteinase K (PK) antigen retrieval to evaluate 4 additional monoclonal antibodies (J18, BBF19, pSyn#64, and D1R1R) in a cohort of 43 confirmed synucleinopathy patients (7 with MSA) and 33 healthy controls. The results showed that PK increased the detection rates for EP1536Y, 81A, and D1R1R, with D1R1R outperforming the others in sensitivity. J18, BBF19, and pSyn#64 exhibited insufficient specificity, limiting their clinical applicability. The improved accuracy with PK treatment and the promising performance of D1R1R mark critical advancements for reliable diagnosis, highlighting the importance of optimizing protocols and validating antibodies for dependable detection of pathological aggregates in skin biopsies.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967894","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

Adequate capture of spatial heterogeneity of Ki-67 proliferative index in meningiomas requires multiple tissue sections. 脑膜瘤中Ki-67增殖指数的空间异质性需要多次组织切片。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-21 DOI: 10.1093/jnen/nlaf043

Ugochukwu Ugwuowo, Bethany Faust, Haiming Tang, Marcello DiStasio

引用次数: 0

Letter to the Editor: Molecularly defined oligodendroglioma evolving to osseous metastases. 致编辑的信：分子定义的少突胶质细胞瘤进化为骨转移瘤。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-04-18 DOI: 10.1093/jnen/nlaf038

Emily Ling-Lin Pai, Yuji Matsumoto, Dan Dou, Shweta Nelluri, Pooja Devi, Salvatore Priori, Nduka Amankulor, Michelle Alonso-Basanta, Omkar Singh, Zied Abdullaev, Kenneth Aldape, Arati Desai, Suyash Mohan, MacLean P Nasrallah

引用次数: 0