{"title":"Re: Article by Machaalani et al. concerning dentate gyrus dysplasia.","authors":"Douglas C Miller","doi":"10.1093/jnen/nlaf011","DOIUrl":"10.1093/jnen/nlaf011","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"444"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557188","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}
Karsten Ruscher, Georgios Michalettos, Sami Abu Hamdeh, Fredrik Clausen, Amber L Nolan, Johanna Flygt, Ilknur Özen, Niklas Marklund
{"title":"Persistent increase of Nogo-A-positive cells and dynamic reduction in oligodendroglia lineage cells in white matter regions following experimental and clinical traumatic brain injury.","authors":"Karsten Ruscher, Georgios Michalettos, Sami Abu Hamdeh, Fredrik Clausen, Amber L Nolan, Johanna Flygt, Ilknur Özen, Niklas Marklund","doi":"10.1093/jnen/nlaf017","DOIUrl":"10.1093/jnen/nlaf017","url":null,"abstract":"<p><p>White matter (WM) disruption and atrophy is a consequence of traumatic brain injury (TBI) and contributes to persisting cognitive impairment. An increased expression of the myelin-associated axonal outgrowth inhibitor Nogo-A and oligodendrocyte pathology might be negatively associated with postinjury WM changes. Here, we analyzed brain tissue from severe TBI patients, obtained by surgical decompression in the early postinjury phase and postmortem brain tissue of long-term TBI survivors and observed an increased number of Nogo-A+ cells in WM tracts such as the corpus callosum (CC). Likewise, the number of Nogo-A+ cells in the CC was increased from day 7 postinjury to 6 months postinjury (mpi) following central fluid percussion injury (cFPI) in mice. In addition, the number of Olig2+ cells in the CC and capsula externa remained constant, while the numbers of Olig2+/CC1+ and GST-π+ mature oligodendrocytes declined throughout the observation time of 18 months. A significantly lower number of Olig2+/CC1+ cells was found in cFPI mice compared to controls at 18 mpi. Persistent vulnerability of oligodendrocytes in combination with dynamic alterations of Nogo-A expression may have implications for the WM atrophy and insufficient recovery observed after TBI.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"423-435"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623408","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}
Julieann C Lee, Amar Gajjar, Melissa R Perrino, Angela Delaney, Christopher L Tinkle, Paul Klimo, Larissa V Furtado, Yen-Chun Liu, Alex Breuer, Soniya N Pinto, Asim K Bag, David W Ellison, Brent A Orr
{"title":"Concurrent Pit-1 and SALL4 staining in primitive component of pituitary blastoma: A case report with clinicopathologic features including Cushing syndrome presentation, germline DICER1 mutation, and significant therapeutic response to chemoradiation.","authors":"Julieann C Lee, Amar Gajjar, Melissa R Perrino, Angela Delaney, Christopher L Tinkle, Paul Klimo, Larissa V Furtado, Yen-Chun Liu, Alex Breuer, Soniya N Pinto, Asim K Bag, David W Ellison, Brent A Orr","doi":"10.1093/jnen/nlae126","DOIUrl":"10.1093/jnen/nlae126","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"436-440"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829012","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}
{"title":"Maximum contrast projection: A powerful tool for biomedical image stack analysis.","authors":"Nat Adamian, Christopher Guirguis, Ansel Link, Nate Jowett, Iván Coto Hernández","doi":"10.1093/jnen/nlaf013","DOIUrl":"10.1093/jnen/nlaf013","url":null,"abstract":"<p><p>Maximum intensity projection is a simple post-hoc dimension reduction approach that yields sharp 2-dimensional images from image stacks but is limited by low signal or high background. Herein, we demonstrated improvement in image contrast using maximum contrast versus maximum intensity projection in 3-dimensional phase-contrast and quantitative phase imaging of frozen cross-sections of murine peripheral nerve. Fresh frozen murine sciatic nerve sections were imaged using 3-dimensional fluorescence, phase-contrast, and quantitative phase microscopy. Images were processed using maximum intensity and maximum contrast projection. Higher image contrast of nerve morphology was obtained when the images were processed with maximum contrast projection. Enhanced image contrast in quantitative phase imaging facilitated label-free multicolor imaging of murine peripheral nerves. Herein, we demonstrate the utility of maximum contrast projection in enhancing image contrast over intensity projection approaches in fluorescence phase-contrast and quantitative phase imaging of nerve histological samples. A user-friendly, open-source Python-based maximum contrast projection algorithm to facilitate the adoption of this technique is provided.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"391-397"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557165","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}
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":"<p><p>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.</p>","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}
{"title":"Authors' response to Dr Miller's letter: \"Machaalani et al. concerning dentate gyrus dysplasia\".","authors":"Rita Machaalani, Michael Rodriguez","doi":"10.1093/jnen/nlaf012","DOIUrl":"10.1093/jnen/nlaf012","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"445-446"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623406","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}
{"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":"<p><p>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.</p>","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}
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
{"title":"EGFR transcript variants: Potential diagnostic biomarker for glioblastoma, IDH-wildtype?","authors":"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","doi":"10.1093/jnen/nlaf041","DOIUrl":"https://doi.org/10.1093/jnen/nlaf041","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031451","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}
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":"<p><p>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.</p>","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}
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":"<p><p>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.</p>","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}