Neuropathic pain arises as a consequence of injury or disease in the peripheral or central nervous system. Clinical cases have shown that spine postoperative chronic neuropathic pain remains a troublesome issue in medical treatment due to the presence of various degrees of peridural fibrosis and different inflammatory factors after spinal surgery. To address this issue, we developed a new neuropathic mice model that successfully simulates the real clinical situation by applying oxidative regenerative cellulose to L5 DRG (dorsal root ganglion). Behavior tests were done by von Fray and thermal stimuli. ELISA and real-time PCR were employed to detect the expression of genes involved in neuropathic pain. This model not only successfully induces chronic pain but also causes membrane thickening, non-neuronal cell recruitment, and a local increase of TNFα and interleukin-6. Additionally, this model did not cause neuron loss in the affected DRG, which mimics the characteristics of sticky tissue-induced neuropathic pain after clinic surgery. Based on this model, we administrated a TNF inhibitor to mice and successfully reduced mechanical allodynia after DRG surgery. In this study, the developed animal model may be a novel platform for delivering neuropathic pain treatments, such as target-based drug discovery or personalized diagnostic approaches.
{"title":"Animal neuropathic pain aroused by conglutinating oxidative regenerative cellulose on dorsal root ganglion.","authors":"Chia-Chi Kung, Shih-Ping Dai, Cheng-Han Yen, Yi-Jui Lee, Shih-Lun Chang, Yi-Ting Fang, Heng-Liang Lin, Chih-Li Chen","doi":"10.1093/jnen/nlae112","DOIUrl":"https://doi.org/10.1093/jnen/nlae112","url":null,"abstract":"<p><p>Neuropathic pain arises as a consequence of injury or disease in the peripheral or central nervous system. Clinical cases have shown that spine postoperative chronic neuropathic pain remains a troublesome issue in medical treatment due to the presence of various degrees of peridural fibrosis and different inflammatory factors after spinal surgery. To address this issue, we developed a new neuropathic mice model that successfully simulates the real clinical situation by applying oxidative regenerative cellulose to L5 DRG (dorsal root ganglion). Behavior tests were done by von Fray and thermal stimuli. ELISA and real-time PCR were employed to detect the expression of genes involved in neuropathic pain. This model not only successfully induces chronic pain but also causes membrane thickening, non-neuronal cell recruitment, and a local increase of TNFα and interleukin-6. Additionally, this model did not cause neuron loss in the affected DRG, which mimics the characteristics of sticky tissue-induced neuropathic pain after clinic surgery. Based on this model, we administrated a TNF inhibitor to mice and successfully reduced mechanical allodynia after DRG surgery. In this study, the developed animal model may be a novel platform for delivering neuropathic pain treatments, such as target-based drug discovery or personalized diagnostic approaches.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516495","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}
Tala Shekarian, Marie-Françoise Ritz, Sabrina Hogan, Tomás A Martins, Philip Schmassmann, Alexandra Gerber, Julien Roux, Deniz Kaymak, Célia Durano, Bettina Burger, Matthias Matter, Gregor Hutter
Glioblastoma (GBM) is a lethal brain tumor without effective treatment options. This study aimed to characterize longitudinal tumor changes in order to find potentially actionable targets to prevent GBM relapse. We extracted RNA and proteins from fresh frozen tumor samples from patient-matched IDHwt WHO grade 4 primary (pGBM) and recurrent (rGBM) tumors for transcriptomics and proteomics analysis. A tissue microarray containing paired tumor samples was processed for spatial transcriptomics analysis. Differentially expressed genes and proteins between pGBM and rGBM were involved in synapse development and myelination. By categorizing patients into short (STTR) and long (LTTR) time-to-lapse, we identified genes/proteins whose expression levels positively or negatively correlated with TTR. In rGBM, expressions of Fcγ receptors (FCGRs) and complement system genes were negatively correlated with TTR, whereas expression of genes involved in DNA methylation was positively correlated with TTR. Spatial transcriptomics of the tumor cells showed enrichment of oligodendrocytes in rGBM. Besides, we observed changes in the myeloid compartment such as a switch from quiescent to activated microglia and an enrichment in B and T cells in rGBM with STTR. Our results uncover a role for activated microglia/macrophages in GBM recurrence and suggest that interfering with these cells may hinder GBM relapse.
胶质母细胞瘤（GBM）是一种致命的脑肿瘤，没有有效的治疗方案。本研究旨在描述肿瘤的纵向变化，从而找到预防 GBM 复发的潜在可操作靶点。我们从与患者匹配的 IDHwt WHO 4 级原发性肿瘤（pGBM）和复发性肿瘤（rGBM）的新鲜冷冻肿瘤样本中提取 RNA 和蛋白质，进行转录组学和蛋白质组学分析。对包含配对肿瘤样本的组织芯片进行了处理，以进行空间转录组学分析。pGBM和rGBM之间表达不同的基因和蛋白质涉及突触的发育和髓鞘化。通过将患者分为短延时（STTR）和长延时（LTTR），我们确定了其表达水平与TTR呈正相关或负相关的基因/蛋白。在rGBM中，Fcγ受体（FCGRs）和补体系统基因的表达与TTR呈负相关，而DNA甲基化相关基因的表达与TTR呈正相关。肿瘤细胞的空间转录组学显示，rGBM 中的少突胶质细胞富集。此外，我们还观察到髓细胞区系的变化，如在患有 STTR 的 rGBM 中，小胶质细胞从静止状态转变为活化状态，以及 B 细胞和 T 细胞的富集。我们的研究结果揭示了活化的小胶质细胞/巨噬细胞在 GBM 复发中的作用，并表明干扰这些细胞可能会阻碍 GBM 复发。
{"title":"Multidimensional analysis of matched primary and recurrent glioblastoma identifies contributors to tumor recurrence influencing time to relapse.","authors":"Tala Shekarian, Marie-Françoise Ritz, Sabrina Hogan, Tomás A Martins, Philip Schmassmann, Alexandra Gerber, Julien Roux, Deniz Kaymak, Célia Durano, Bettina Burger, Matthias Matter, Gregor Hutter","doi":"10.1093/jnen/nlae108","DOIUrl":"https://doi.org/10.1093/jnen/nlae108","url":null,"abstract":"<p><p>Glioblastoma (GBM) is a lethal brain tumor without effective treatment options. This study aimed to characterize longitudinal tumor changes in order to find potentially actionable targets to prevent GBM relapse. We extracted RNA and proteins from fresh frozen tumor samples from patient-matched IDHwt WHO grade 4 primary (pGBM) and recurrent (rGBM) tumors for transcriptomics and proteomics analysis. A tissue microarray containing paired tumor samples was processed for spatial transcriptomics analysis. Differentially expressed genes and proteins between pGBM and rGBM were involved in synapse development and myelination. By categorizing patients into short (STTR) and long (LTTR) time-to-lapse, we identified genes/proteins whose expression levels positively or negatively correlated with TTR. In rGBM, expressions of Fcγ receptors (FCGRs) and complement system genes were negatively correlated with TTR, whereas expression of genes involved in DNA methylation was positively correlated with TTR. Spatial transcriptomics of the tumor cells showed enrichment of oligodendrocytes in rGBM. Besides, we observed changes in the myeloid compartment such as a switch from quiescent to activated microglia and an enrichment in B and T cells in rGBM with STTR. Our results uncover a role for activated microglia/macrophages in GBM recurrence and suggest that interfering with these cells may hinder GBM relapse.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468201","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}
Jacob A Schroeder, Mohammed Sabawi, Amr H Masaadeh, Kathryn L Eschbacher, Nitesh Shekhrajka, Márcio Luís Duarte, Leonardo Furtado Freitas
{"title":"Acquired intradiploic epidermoid cyst: A rare case report with literature review.","authors":"Jacob A Schroeder, Mohammed Sabawi, Amr H Masaadeh, Kathryn L Eschbacher, Nitesh Shekhrajka, Márcio Luís Duarte, Leonardo Furtado Freitas","doi":"10.1093/jnen/nlae106","DOIUrl":"https://doi.org/10.1093/jnen/nlae106","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468200","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}
Kentaro Ohara, Majd Al Assaad, Samantha N McNulty, Hussein Alnajar, Andrea Sboner, David C Wilkes, Feng He, Jenny Zhaoying Xiang, Susan Mathew, Olivier Elemento, David J Pisapia, Juan Miguel Mosquera
{"title":"Detection of rare and novel gene fusions in patients with diffuse glioma: An institutional retrospective study.","authors":"Kentaro Ohara, Majd Al Assaad, Samantha N McNulty, Hussein Alnajar, Andrea Sboner, David C Wilkes, Feng He, Jenny Zhaoying Xiang, Susan Mathew, Olivier Elemento, David J Pisapia, Juan Miguel Mosquera","doi":"10.1093/jnen/nlae105","DOIUrl":"https://doi.org/10.1093/jnen/nlae105","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348692","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}
Steven N Schwartz, Danielle K Stamer, Elliott Jiles, Hemant Varma, Rafael A Vega, Bartholomew White
{"title":"DNA methylation profiling in a case of papillary tumor of the pineal region.","authors":"Steven N Schwartz, Danielle K Stamer, Elliott Jiles, Hemant Varma, Rafael A Vega, Bartholomew White","doi":"10.1093/jnen/nlae099","DOIUrl":"https://doi.org/10.1093/jnen/nlae099","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348693","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}
Fouad El-Dana, Kenneth Aldape, Zied Abdullaev, Sameer Anil Sheth, Jacob Mandel, Hsiang-Chih Lu
{"title":"Low-grade glial/glioneuronal tumor with YAP1::FAM118B fusion: A novel molecular finding.","authors":"Fouad El-Dana, Kenneth Aldape, Zied Abdullaev, Sameer Anil Sheth, Jacob Mandel, Hsiang-Chih Lu","doi":"10.1093/jnen/nlae103","DOIUrl":"https://doi.org/10.1093/jnen/nlae103","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289639","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}
Regina R Reimann, Dorothee Gramatzki, Andrea Bink, Jürgen Hench, Stephan Frank, Martina Haberecker, Tibor Hortobagyi, Kristof Egervari, Doron Merkler, Kenneth Aldape, Michael Weller
{"title":"Long survival in a patient with fumarate hydratase mutation-associated glioma.","authors":"Regina R Reimann, Dorothee Gramatzki, Andrea Bink, Jürgen Hench, Stephan Frank, Martina Haberecker, Tibor Hortobagyi, Kristof Egervari, Doron Merkler, Kenneth Aldape, Michael Weller","doi":"10.1093/jnen/nlae100","DOIUrl":"https://doi.org/10.1093/jnen/nlae100","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289638","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":"Correction to: Abstracts of the 100th Annual Meeting June 6-9, 2024 Olympic Valley, California.","authors":"","doi":"10.1093/jnen/nlae102","DOIUrl":"10.1093/jnen/nlae102","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"1088"},"PeriodicalIF":3.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289637","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}
Qian-Qian Li,Qi Yu,Zhi-Yi Liu,Qin Zhang,Meng-Yuan Li,Yan Hu
Sevoflurane (Sevo) is widely used for general anesthesia during pregnancy. Emerging evidence indicates that maternal Sevo exposure can trigger developmental neurotoxicity in the offspring. Nonetheless, the underlying mechanisms need further investigation. Pregnant Sprague-Dawley rats on gestational day 18 were exposed to 3.5% Sevo to induce the rat model of neurotoxicity. TAK-242, a TLR4 inhibitor, was administrated to inhibit the signaling transduction. Hippocampal tissues of rat offspring were harvested for immunohistochemical staining, TUNEL staining, Western blotting, ELISA, and measurement of oxidative stress-related markers. Serum samples were collected to evaluate lipid metabolism-associated factors. Morris water maze was implemented to test the cognitive function of offspring rats. Rat hippocampal neurons were isolated to elucidate the effect of TAK-242 on the BDNF/TrkB/CREB signaling in vitro. The results showed that maternal Sevo exposure during the third trimester induced neuroinflammation, lipid metabolism disturbance, and oxidative stress, and impaired the spatial learning and memory of rat offspring. Sevo upregulated TLR4 and impeded BDNF/TrkB/CREB signaling transduction in the hippocampus of rat offspring; TAK-242 administration reversed these effects. In conclusion, Sevo anesthesia during late gestation impairs the learning and memory ability of rat offspring possibly by promoting neuroinflammation and disturbing lipid metabolism via the TLR4/BDNF/TrkB/CREB pathway.
{"title":"Sevoflurane anesthesia during late gestation induces cognitive disorder in rat offspring via the TLR4/BDNF/TrkB/CREB pathway.","authors":"Qian-Qian Li,Qi Yu,Zhi-Yi Liu,Qin Zhang,Meng-Yuan Li,Yan Hu","doi":"10.1093/jnen/nlae096","DOIUrl":"https://doi.org/10.1093/jnen/nlae096","url":null,"abstract":"Sevoflurane (Sevo) is widely used for general anesthesia during pregnancy. Emerging evidence indicates that maternal Sevo exposure can trigger developmental neurotoxicity in the offspring. Nonetheless, the underlying mechanisms need further investigation. Pregnant Sprague-Dawley rats on gestational day 18 were exposed to 3.5% Sevo to induce the rat model of neurotoxicity. TAK-242, a TLR4 inhibitor, was administrated to inhibit the signaling transduction. Hippocampal tissues of rat offspring were harvested for immunohistochemical staining, TUNEL staining, Western blotting, ELISA, and measurement of oxidative stress-related markers. Serum samples were collected to evaluate lipid metabolism-associated factors. Morris water maze was implemented to test the cognitive function of offspring rats. Rat hippocampal neurons were isolated to elucidate the effect of TAK-242 on the BDNF/TrkB/CREB signaling in vitro. The results showed that maternal Sevo exposure during the third trimester induced neuroinflammation, lipid metabolism disturbance, and oxidative stress, and impaired the spatial learning and memory of rat offspring. Sevo upregulated TLR4 and impeded BDNF/TrkB/CREB signaling transduction in the hippocampus of rat offspring; TAK-242 administration reversed these effects. In conclusion, Sevo anesthesia during late gestation impairs the learning and memory ability of rat offspring possibly by promoting neuroinflammation and disturbing lipid metabolism via the TLR4/BDNF/TrkB/CREB pathway.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":"29 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259695","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}
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