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":"<p><p>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.</p>","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}
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":"<p><p>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.</p>","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}
Gonzalo Hernandez Gamero, Evelina Miele, Andrea Mafficini, Lucrezia Ghione, Sara Patrizi, Lucia Pedace, Serena Ammendola, Valeria Barresi
{"title":"Shift of DNA methylation class may occur on recurrence of pleomorphic xanthoastrocytoma.","authors":"Gonzalo Hernandez Gamero, Evelina Miele, Andrea Mafficini, Lucrezia Ghione, Sara Patrizi, Lucia Pedace, Serena Ammendola, Valeria Barresi","doi":"10.1093/jnen/nlaf061","DOIUrl":"https://doi.org/10.1093/jnen/nlaf061","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150746","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}
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":"<p><p>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.</p>","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}
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":"<p><p>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.</p>","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}
Nadeem Toodayan, Joseph Stockwell, Judith Spies, Joanne Sy, Rajiv Wijesinghe, Benjamin Nham
{"title":"Biopsy-proven granulomatous neuromyopathy in a case of Blau syndrome.","authors":"Nadeem Toodayan, Joseph Stockwell, Judith Spies, Joanne Sy, Rajiv Wijesinghe, Benjamin Nham","doi":"10.1093/jnen/nlaf056","DOIUrl":"https://doi.org/10.1093/jnen/nlaf056","url":null,"abstract":"<p><p>A 37-year-old woman with Blau syndrome was extensively investigated for a rapidly progressive ascending sensorimotor polyneuropathy initially thought to be Guillain-Barré syndrome. The patient's symptoms progressed despite intravenous immunoglobulin therapy, with increasingly asymmetric involvement suggestive of mononeuritis multiplex, a pattern confirmed on nerve conduction studies. As her symptoms failed to respond to treatment, the question arose whether or not granulomatous inflammation in Blau syndrome (congenital autoinflammatory granulomatous polyarthritis, dermatitis, and uveitis) might be responsible for this presentation. A review of the published literature on Blau syndrome suggested this to be highly unlikely, but sural nerve and quadriceps muscle biopsies revealed active granulomatous inflammation of affected axons and muscles. To our knowledge, histopathological involvement of these tissues has not been reported previously in Blau syndrome.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127945","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}
Bilge Yaşar, Bahattin Tanrıkulu, Ayça Erşen Danyeli, M Memet Özek
{"title":"Aggressive behavior in a molecularly benign tumor: The diagnostic odyssey of a pediatric pilocytic astrocytoma with initial high-grade histologic features and rapid recurrence.","authors":"Bilge Yaşar, Bahattin Tanrıkulu, Ayça Erşen Danyeli, M Memet Özek","doi":"10.1093/jnen/nlaf055","DOIUrl":"https://doi.org/10.1093/jnen/nlaf055","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127942","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":"Phospholipase C epsilon 1 aggravates β-amyloid-associated cognitive impairments and pyroptosis through activating the RAC1-STAT3 pathway in Alzheimer disease models.","authors":"Lijuan Pei, Wenjuan Hu, Li Wang, Hongbin Cai","doi":"10.1093/jnen/nlaf048","DOIUrl":"https://doi.org/10.1093/jnen/nlaf048","url":null,"abstract":"<p><p>Increased phospholipase C epsilon 1 (PLCE1) gene expression has been observed in patients with Alzheimer disease (AD), but its roles in AD remain unclear. This study aimed to explore the effects of PLCE1 expression in AD models. Rats were divided into 4 groups: sham+AAV-shNC (negative control), sham+AAV-shPLCE1, Aβ+AAV-shNC, and Aβ + AAV-shPLCE1. To investigate the effects of PLCE1 expression following β-amyloid administration, its expression was measured at both the mRNA and protein levels. Cognitive function was assessed using the Morris water maze. Immunofluorescence and Nissl staining of cerebral cortical tissues demonstrated that PLCE1 downregulation alleviated β-amyloid-induced brain injury. TUNEL, Western blot, and Enzyme-linked Immunosorbent Assay (ELISA) assays also showed that PLCE1 downregulation inhibited pyroptosis and inflammatory markers in the rats and in SH-SY5Y neuroblastoma cells. Using MTT, TUNEL, Western blot, and ELISA assays, we found that upregulation of the GTPase RAC1, which belongs to the RAS superfamily of small GTP-binding proteins, reversed the neuroprotective effect of PLCE1 downregulation. Together, this study suggests that PLCE1 may worsen AD by activating the STAT3 pathway through RAC1 upregulation. Overall, PLCE1 may exacerbate β-amyloid-induced cognitive impairments and pyroptosis via the RAC1-STAT3 pathway in AD patients.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127949","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}
Sara Hayama, Chase Hwang, Christopher Lum, Jane Uyehara-Lock, Wichit Sae-Ow, Koah Vierkoetter, Brock Kaya
{"title":"Metastases to dysplastic cerebellar gangliocytomas.","authors":"Sara Hayama, Chase Hwang, Christopher Lum, Jane Uyehara-Lock, Wichit Sae-Ow, Koah Vierkoetter, Brock Kaya","doi":"10.1093/jnen/nlaf054","DOIUrl":"https://doi.org/10.1093/jnen/nlaf054","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111037","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":"Biological role and clinicopathological significance of leucine-rich α-2 glycoprotein 1 in the glioblastoma microenvironment.","authors":"Takuya Furuta, Hiroaki Miyoshi, Mayuko Moritsubo, Riho Nakajima, Tetsuya Negoto, Hideo Nakamura, Motohiro Morioka, Yasuo Uchida, Sumio Ohtsuki, Mitsutoshi Nakada","doi":"10.1093/jnen/nlaf049","DOIUrl":"https://doi.org/10.1093/jnen/nlaf049","url":null,"abstract":"<p><p>Pseudoprogression, often misinterpreted as glioblastoma progression on MRI, results from treatment-induced inflammation and can resolve without additional intervention. This study investigated the role of leucine-rich α-2 glycoprotein 1 (LRG1) in the glioblastoma microenvironment. Leucine-rich α-2 glycoprotein 1 is associated with inflammation and prognosis in various diseases and its blood concentrations reflect disease-related inflammation. We focused on LRG1 expression in reactive astrocytes and assessed its potential as a biomarker for glioblastoma pseudoprogression. Cases with high LRG1 expression exhibited a distinct molecular profile, with increased angiogenesis-related gene expression and reduced stem cell-related gene activity, underscoring its dual role in tumor biology and progression. In vitro experiments demonstrated that LRG1 suppressed tumor cell invasion, supporting its inverse correlation with tumor cell stemness. Immunohistochemical analysis revealed that astrocytic LRG1 was associated with heightened peritumoral inflammation, characterized by CD8+ T-cell infiltration at the tumor periphery; this correlated with higher pseudoprogression rates and poorer prognosis. By providing a histopathological marker for pseudoprogression, LRG1 complements current imaging modalities and offers a novel approach to addressing unresolved diagnostic challenges in glioblastoma. These findings establish LRG1 as a promising biomarker that could aid clinicians in distinguishing pseudoprogression from true progression, ultimately enhancing personalized treatment strategies for glioblastoma patients.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026613","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}