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A case of a pilocytic astrocytoma with histological features of anaplasia and unprecedent genetic alterations. 一例毛细胞星形细胞瘤,具有间变性和前所未有的遗传改变的组织学特征。
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-04-01 Epub Date: 2023-10-01 DOI: 10.1111/neup.12946
Mayuko Moritsubo, Takuya Furuta, Tetsuya Negoto, Hideo Nakamura, Yusuke Uchiyama, Motohiro Morioka, Koichi Oshima, Yasuo Sugita

We report a case of pediatric glioma with uncommon imaging, morphological, and genetic features. A one-year-old boy incidentally presented with a tumor in the fourth ventricle. The tumor was completely resected surgically and investigated pathologically. The mostly circumscribed tumor had piloid features but primitive and anaplastic histology, such as increasing cellularity and mitosis. The Ki-67 staining index was 25% at the hotspot. KIAA1549::BRAF fusion and KIAA1549 partial deletions were detected by direct PCR, supported by Sanger sequencing. To the best of our knowledge, this is the first report of a glioma with both deletion of KIAA1549 p.P1771_P1899 and fusion of KIAA1549::BRAF. The tumor could not be classified using DNA methylome analysis. The present tumor fell into the category of pilocytic astrocytoma with histological features of anaplasia (aPA). Further studies are needed to establish pediatric aPA.

我们报告了一例儿童胶质瘤,其影像学、形态学和遗传学特征不常见。一名一岁男孩偶然在第四脑室出现肿瘤。肿瘤经手术完全切除,并经病理学检查。大多数局限性肿瘤具有毛状特征,但组织学原始且间变性,如细胞数量增加和有丝分裂。Ki-67染色指数在热点处为25%。KIAA1549::BRAF融合和KIAA1549部分缺失通过直接PCR检测,Sanger测序支持。据我们所知,这是第一例同时缺失KIAA1549 p.P1771_P1899和融合KIAA1549::BRAF的神经胶质瘤报告。DNA甲基组分析无法对肿瘤进行分类。目前的肿瘤属于毛细胞星形细胞瘤,具有间变性(aPA)的组织学特征。需要进一步的研究来建立儿科aPA。
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引用次数: 0
Senile plaque-associated transactive response DNA-binding protein 43 in Alzheimer's disease: A case report spanning 16 years of memory loss. 阿尔茨海默病中与老年斑相关的转录反应 DNA 结合蛋白 43:跨越 16 年记忆丧失的病例报告。
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-04-01 Epub Date: 2023-07-31 DOI: 10.1111/neup.12938
Arenn F Carlos, Shunsuke Koga, Neill R Graff-Radford, Matthew C Baker, Rosa Rademakers, Owen A Ross, Dennis W Dickson, Keith A Josephs

Transactive response DNA-binding protein 43 (TDP-43) pathological inclusions are found in frontotemporal lobar degeneration (FTLD-TDP) and Alzheimer's disease (AD-TDP). While clinically different, TDP-43 inclusions in FTLD-TDP and AD can have similar morphological characteristics. However, TDP-43 colocalizing with tau and forming "apple-bite" or "flame-shaped" neuronal cytoplasmic inclusions (NCI) are only found in AD-TDP. Here, we describe a case with AD and neuritic plaque-associated TDP-43. The patient was a 96-year-old right-handed Caucasian woman who had developed a slowly progressive amnestic syndrome compatible with typical AD at age 80. Genetic testing revealed APOE ε3/ε4, GRN r5848 CT, and MAPT H1/H2 genotype. Consistent with the old age at onset and long disease duration, limbic-predominant AD was found at autopsy, with high hippocampal yet low cortical neurofibrillary tangle (NFT) counts. Hippocampal and amygdala sclerosis were present. Immunohistochemistry for phospho-TDP-43 showed NCIs, dystrophic neurites, and rare neuronal intranuclear inclusions consistent with FTLD-TDP type A, as well as tau NFT-associated TDP-43 inclusions. These were frequent in the amygdala, entorhinal cortex, hippocampus, occipitotemporal gyrus, and inferior temporal gyrus but sparse in the mid-frontal cortex. Additionally, there were TDP-43-immunoreactive inclusions forming plaque-like structures in the molecular layer of the dentate fascia of the hippocampus. The presence of neuritic plaques in the same region was confirmed using thioflavin-S fluorescent microscopy and immunohistochemistry for phospho-tau. Double labeling immunofluorescence showed colocalization of TDP-43 and tau within neuritic plaques. Other pathologies included mild Lewy body pathology predominantly affecting the amygdala and olfactory bulb, aging-related tau astrogliopathy, and mixed small vessel disease (arteriolosclerosis and amyloid angiopathy) with several cortical microinfarcts. In conclusion, we have identified TDP-43 colocalizing with tau in neuritic plaques in AD, which expands the association of TDP-43 and tau in AD beyond NFTs. The clinical correlate of this plaque-associated TDP-43 appears to be a slowly progressive amnestic syndrome.

在额颞叶变性(FTLD-TDP)和阿尔茨海默病(AD-TDP)中发现了转录反应DNA结合蛋白43(TDP-43)病理包涵体。虽然临床表现不同,但 FTLD-TDP 和 AD 中的 TDP-43 包涵体可能具有相似的形态特征。然而,TDP-43与tau共聚焦并形成 "苹果咬合 "或 "火焰形 "神经元胞浆包涵体(NCI)仅见于AD-TDP。在此,我们描述了一例 AD 和神经斑块相关 TDP-43 的病例。患者是一名 96 岁的右撇子高加索女性,80 岁时出现了与典型 AD 相似的缓慢进展性失忆综合征。基因检测显示她患有 APOE ε3/ε4、GRN r5848 CT 和 MAPT H1/H2 基因型。与发病年龄大、病程长相一致的是,尸检时发现了以边缘为主的AD,海马计数高而皮质神经纤维缠结(NFT)计数低。存在海马和杏仁核硬化。磷酸化-TDP-43免疫组化显示出NCIs、萎缩性神经元、与FTLD-TDP A型一致的罕见神经元核内包涵体以及与tau NFT相关的TDP-43包涵体。在杏仁核、内视网膜皮层、海马、枕颞回和颞下回等部位经常出现这些包涵体,但在额叶中层皮层则很少见。此外,在海马齿状筋膜的分子层中存在 TDP-43 免疫反应性包涵体,形成斑块样结构。使用硫黄素-S荧光显微镜和磷酸化-tau免疫组化法证实了同一区域存在神经斑块。双标记免疫荧光显示,TDP-43和tau在神经斑块内共定位。其他病变包括主要影响杏仁核和嗅球的轻度路易体病变、与衰老相关的tau星形胶质细胞病变以及伴有数个皮质微梗塞的混合性小血管疾病(动脉硬化和淀粉样血管病)。总之,我们在 AD 的神经斑块中发现了 TDP-43 与 tau 的共聚焦,这将 TDP-43 与 tau 在 AD 中的关联扩展到了 NFTs 之外。这种斑块相关的TDP-43的临床相关性似乎是一种缓慢进展的失忆综合征。
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引用次数: 0
O6 -methylguanine methyltransferase promoter methylation status of glioblastoma cell line clonal population. 胶质母细胞瘤细胞系克隆群体的 O6 -甲基鸟嘌呤甲基转移酶启动子甲基化状况。
IF 1.3 4区 医学 Q4 CLINICAL NEUROLOGY Pub Date : 2024-02-01 Epub Date: 2023-06-29 DOI: 10.1111/neup.12931
Mitsuhiro Anan, Rolando Fausto Del Maestro, Nobuhiro Hata, Minoru Fujiki

Glioblastoma (GBM) remains a treatment-resistant malignant brain tumor in large part because of its genetic heterogeneity and epigenetic plasticity. In this study, we investigated the epigenetic heterogeneity of GBM by evaluating the methylation status of the O6 -methylguanine methyltransferase (MGMT) promoter in individual clones of a single cell derived from GBM cell lines. The U251 and U373 GBM cell lines, from the Brain Tumour Research Centre of the Montreal Neurological Institute, were used for the experiments. To evaluate the methylation status of the MGMT promoter, pyrosequencing and methylation-specific PCR (MSP) were used. Moreover, mRNA and protein expression levels of MGMT in the individual GBM clones were evaluated. The HeLa cell line, which hyper-expresses MGMT, was used as control. A total of 12 U251 and 12 U373 clones were isolated. The methylation status of 83 of 97 CpG sites in the MGMT promoter were evaluated by pyrosequencing, and 11 methylated CpG sites and 13 unmethylated CpG sites were evaluated by MSP. The methylation status by pyrosequencing was relatively high at CpG sites 3-8, 20-35, and 7-83, in both the U251 and U373 clones. Neither MGMT mRNA nor protein was detected in any clone. These findings demonstrate tumor heterogeneity among individual clones derived from a single GBM cell. MGMT expression may be regulated, not only by methylation of the MGMT promoter but by other factors as well. Further studies are needed to clarify the mechanisms underlying the epigenetic heterogeneity and plasticity of GBM.

胶质母细胞瘤(GBM)仍然是一种耐药的恶性脑肿瘤,这在很大程度上是因为它具有遗传异质性和表观遗传可塑性。在这项研究中,我们通过评估源自 GBM 细胞系的单个细胞克隆中 O6 -甲基鸟嘌呤甲基转移酶(MGMT)启动子的甲基化状态,研究了 GBM 的表观遗传异质性。实验使用了蒙特利尔神经研究所脑肿瘤研究中心的 U251 和 U373 GBM 细胞系。为了评估 MGMT 启动子的甲基化状态,使用了热测序和甲基化特异性 PCR (MSP)。此外,还评估了各个 GBM 克隆中 MGMT 的 mRNA 和蛋白表达水平。MGMT高表达的HeLa细胞系被用作对照。共分离出 12 个 U251 和 12 个 U373 克隆。通过热测序评估了 MGMT 启动子 97 个 CpG 位点中 83 个位点的甲基化状态,通过 MSP 评估了 11 个甲基化 CpG 位点和 13 个未甲基化 CpG 位点。在 U251 和 U373 克隆中,热释光测序法对 CpG 位点 3-8、20-35 和 7-83 的甲基化状态进行了评估。在任何克隆中都没有检测到 MGMT mRNA 或蛋白质。这些发现表明,来自单个 GBM 细胞的克隆之间存在肿瘤异质性。MGMT 的表达可能不仅受 MGMT 启动子甲基化的调控,还受其他因素的调控。要弄清 GBM 表观遗传异质性和可塑性的内在机制,还需要进一步的研究。
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引用次数: 0
Erdheim-Chester disease of brain parenchyma without any systemic involvement: A case report and review of literature. 埃尔德海姆-切斯特脑实质病(Erdheim-Chester disease),无全身受累:病例报告和文献综述
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-02-01 Epub Date: 2023-06-26 DOI: 10.1111/neup.12930
Merve Aktan Suzgun, Elif Everest, Selin Kucukyurt, Melih Tutuncu, Ugur Uygunoglu, Ahmet Emre Eskazan, Ugur Ture, Herbert Budka, Aydin Sav, Aksel Siva

Erdheim-Chester disease is a non-Langerhans cell histiocytosis syndrome characterised by histiocytic infiltration of different organs and systems in the body. Erdheim-Chester disease with isolated central nervous system (CNS) involvement causes diagnostic difficulties due to the absence of systemic findings and may result in misdiagnosis and inaccurate treatment choices. The case discussed in this report exemplifies how challenging it is to diagnose Erdheim-Chester disease with isolated CNS involvement. This case, which presented with progressive pyramidocerebellar syndrome, was clinically and radiologically resistant to all immunosuppressive and immunomodulatory treatments administered. The presence of false negative results in repeated histopathological investigations and the absence of evidence for systemic disease hindered the diagnosis and treatment work-up. In this study, we reviewed and discussed the prominent features of the presented case in light of the relevant literature.

埃尔德海姆-切斯特病是一种非朗格汉斯细胞组织细胞增生症综合征,其特征是组织细胞浸润人体的不同器官和系统。埃尔德海姆-切斯特病患者的中枢神经系统(CNS)孤立受累,由于没有全身性的发现,会给诊断带来困难,并可能导致误诊和治疗选择的不准确。本报告中讨论的病例充分说明了诊断孤立性中枢神经系统受累的埃尔德海姆-切斯特病是多么具有挑战性。该病例表现为进行性锥体小脑综合征,在临床和影像学上对所有免疫抑制和免疫调节治疗均无效。反复组织病理学检查的假阴性结果和全身性疾病证据的缺失阻碍了诊断和治疗工作。在本研究中,我们结合相关文献回顾并讨论了该病例的突出特点。
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引用次数: 0
Balamuthia mandrillaris amoebic encephalitis mimicking tuberculous meningitis. 模仿结核性脑膜炎的山魈阿米巴脑炎(Balamuthia mandrillaris amoebic encephalitis)。
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-02-01 Epub Date: 2023-06-28 DOI: 10.1111/neup.12932
Yoya Ono, Kazuhiro Higashida, Kanako Yamanouchi, Shusuke Nomura, Yuki Hanamatsu, Chiemi Saigo, Nobuyuki Tetsuka, Takayoshi Shimohata

A 76-year-old female with no apparent immunosuppressive conditions and no history of exposure to freshwater and international travel presented with headache and nausea 3 weeks before the presentation. On admission, her consciousness was E4V4V6. Cerebrospinal fluid analysis showed pleocytosis with mononuclear cell predominance, elevated protein, and decreased glucose. Despite antibiotic and antiviral therapy, her consciousness and neck stiffness gradually worsened, right eye-movement restriction appeared, and the right direct light reflex became absent. Brain magnetic resonance imaging revealed hydrocephalus in the inferior horn of the left lateral ventricle and meningeal enhancement around the brainstem and cerebellum. Tuberculous meningitis was suspected, and pyrazinamide, ethambutol, rifampicin, isoniazid, and dexamethasone were started. In addition, endoscopic biopsy was performed from the white matter around the inferior horn of the left lateral ventricle to exclude brain tumor. A brain biopsy specimen revealed eosinophilic round cytoplasm with vacuoles around blood vessels, and we diagnosed with amoebic encephalitis. We started azithromycin, flucytosine, rifampicin, and fluconazole, but her symptoms did not improve. She died 42 days after admission. In autopsy, the brain had not retained its structure due to autolysis. Hematoxylin and eosin staining of her brain biopsy specimen showed numerous amoebic cysts in the perivascular brain tissue. Analysis of the 16S ribosomal RNA region of amoebas from brain biopsy and autopsy specimens revealed a sequence consistent with Balamuthia mandrillaris. Amoebic meningoencephalitis can present with features characteristic of tuberculous meningitis, such as cranial nerve palsies, hydrocephalus, and basal meningeal enhancement. Difficulties in diagnosing amoebic meningoencephalitis are attributed to the following factors: (1) excluding tuberculous meningitis by microbial testing is difficult, (2) amoebic meningoencephalitis has low incidence and can occur without obvious exposure history, (3) invasive brain biopsy is essential in diagnosing amoebic meningoencephalitis. We should recognize the possibility of amoebic meningoencephalitis when evidence of tuberculosis meningitis cannot be demonstrated.

一名 76 岁女性,无明显免疫抑制症状,无淡水接触史和国际旅行史,发病前 3 周出现头痛和恶心。入院时,她的意识为 E4V4V6。脑脊液分析显示单核细胞为主的多形核细胞增多,蛋白质升高,葡萄糖降低。尽管接受了抗生素和抗病毒治疗,但她的意识和颈部僵硬逐渐恶化,右眼活动受限,右侧直视光反射消失。脑磁共振成像显示左侧外脑室下角有脑积水,脑干和小脑周围有脑膜强化。医生怀疑是结核性脑膜炎,并开始使用吡嗪酰胺、乙胺丁醇、利福平、异烟肼和地塞米松。此外,为了排除脑肿瘤,还对左侧外脑室下角周围的白质进行了内窥镜活检。脑活检标本显示嗜酸性圆形胞浆,血管周围有空泡,我们诊断为阿米巴脑炎。我们开始使用阿奇霉素、氟尿嘧啶、利福平和氟康唑,但她的症状没有改善。她在入院 42 天后死亡。尸检结果显示,大脑因自溶而未保留其结构。对她的脑活检标本进行苏木精和伊红染色后发现,血管周围的脑组织中有许多阿米巴囊肿。对脑活检标本和尸检标本中阿米巴的 16S 核糖体 RNA 区域进行分析后发现,其序列与山魈巴拉穆氏虫一致。阿米巴脑膜脑炎可表现出结核性脑膜炎的特征,如颅神经麻痹、脑积水和基底脑膜强化。诊断阿米巴脑膜脑炎的困难可归因于以下因素:(1)很难通过微生物检测排除结核性脑膜炎;(2)阿米巴脑膜脑炎发病率低,可在无明显接触史的情况下发生;(3)侵入性脑活检对诊断阿米巴脑膜脑炎至关重要。在无法证明结核性脑膜炎的证据时,我们应认识到阿米巴脑膜脑炎的可能性。
{"title":"Balamuthia mandrillaris amoebic encephalitis mimicking tuberculous meningitis.","authors":"Yoya Ono, Kazuhiro Higashida, Kanako Yamanouchi, Shusuke Nomura, Yuki Hanamatsu, Chiemi Saigo, Nobuyuki Tetsuka, Takayoshi Shimohata","doi":"10.1111/neup.12932","DOIUrl":"10.1111/neup.12932","url":null,"abstract":"<p><p>A 76-year-old female with no apparent immunosuppressive conditions and no history of exposure to freshwater and international travel presented with headache and nausea 3 weeks before the presentation. On admission, her consciousness was E4V4V6. Cerebrospinal fluid analysis showed pleocytosis with mononuclear cell predominance, elevated protein, and decreased glucose. Despite antibiotic and antiviral therapy, her consciousness and neck stiffness gradually worsened, right eye-movement restriction appeared, and the right direct light reflex became absent. Brain magnetic resonance imaging revealed hydrocephalus in the inferior horn of the left lateral ventricle and meningeal enhancement around the brainstem and cerebellum. Tuberculous meningitis was suspected, and pyrazinamide, ethambutol, rifampicin, isoniazid, and dexamethasone were started. In addition, endoscopic biopsy was performed from the white matter around the inferior horn of the left lateral ventricle to exclude brain tumor. A brain biopsy specimen revealed eosinophilic round cytoplasm with vacuoles around blood vessels, and we diagnosed with amoebic encephalitis. We started azithromycin, flucytosine, rifampicin, and fluconazole, but her symptoms did not improve. She died 42 days after admission. In autopsy, the brain had not retained its structure due to autolysis. Hematoxylin and eosin staining of her brain biopsy specimen showed numerous amoebic cysts in the perivascular brain tissue. Analysis of the 16S ribosomal RNA region of amoebas from brain biopsy and autopsy specimens revealed a sequence consistent with Balamuthia mandrillaris. Amoebic meningoencephalitis can present with features characteristic of tuberculous meningitis, such as cranial nerve palsies, hydrocephalus, and basal meningeal enhancement. Difficulties in diagnosing amoebic meningoencephalitis are attributed to the following factors: (1) excluding tuberculous meningitis by microbial testing is difficult, (2) amoebic meningoencephalitis has low incidence and can occur without obvious exposure history, (3) invasive brain biopsy is essential in diagnosing amoebic meningoencephalitis. We should recognize the possibility of amoebic meningoencephalitis when evidence of tuberculosis meningitis cannot be demonstrated.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10071537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Documented growth of an intracranial capillary hemangioma: A case report. 颅内毛细血管瘤生长记录:病例报告。
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-02-01 Epub Date: 2023-07-04 DOI: 10.1111/neup.12933
Abigale D MacLellan, Alexander S Easton, Rufus Alubankudi, Gwynedd E Pickett

Intracranial capillary hemangiomas in adults are rare, and diagnosis can be challenging. Hemangiomas, in general (and particularly in the skin), are more often noted in the pediatric population. Due to the lack of imaging undertaken in the presymptomatic phase, the literature provides few clues on the rate of growth of these unusual tumors. Therefore, we report a case of a 64-year-old man with a medical history of Lyme disease who presented with exhaustion and confusion. Imaging demonstrated an intra-axial lesion with vascularity in the posterior right temporal lobe, raising the possibility of a glioma. Imaging two years prior revealed a very small lesion in the same location. The patient underwent a craniectomy, total resection of the lesion was completed, and his symptoms of confusion resolved. Biopsy revealed a capillary hemangioma composed of small vascular channels lined by endothelial cells and pericytes without smooth muscle. Features of glioma, vascular neoplasms or neuroborreliosis (cerebral Lyme disease) were not identified. Our case documents the growth over two years of a rare intracranial capillary hemangioma in an older adult male.

成人颅内毛细血管瘤非常罕见,诊断也很困难。一般来说,血管瘤(尤其是皮肤血管瘤)多见于儿童。由于缺乏无症状期的影像学检查,文献很少提供有关这些异常肿瘤生长速度的线索。因此,我们报告了一例有莱姆病病史的 64 岁男性患者的病例。影像学检查显示,他的右颞叶后部有一个带有血管的轴内病变,这引起了胶质瘤的可能性。两年前的影像学检查显示,同一位置有一个非常小的病灶。患者接受了颅骨切除术,完成了病灶的全部切除,精神错乱的症状也随之缓解。活组织检查显示,这是一个毛细血管瘤,由内皮细胞和周细胞构成的小血管通道组成,没有平滑肌。没有发现胶质瘤、血管肿瘤或神经源性疾病(脑莱姆病)的特征。我们的病例记录了一名老年男性颅内毛细血管瘤生长两年多的罕见病例。
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引用次数: 0
Correction to "MicroRNA-221 targeting PI3-K/Akt signaling axis induces cell proliferation and BCNU resistance in human glioblastoma". 更正“靶向PI3-K/Akt信号轴的MicroRNA-221诱导人胶质母细胞瘤中的细胞增殖和BCNU耐药性”。
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-02-01 Epub Date: 2023-09-20 DOI: 10.1111/neup.12943
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引用次数: 0
Astrocytes in ischemic stroke: Crosstalk in central nervous system and therapeutic potential. 缺血性中风中的星形胶质细胞:中枢神经系统的相互影响与治疗潜力
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-02-01 Epub Date: 2023-06-21 DOI: 10.1111/neup.12928
Jueling Liu, Yuying Guo, Yunsha Zhang, Xiaoxiao Zhao, Rong Fu, Shengyu Hua, Shixin Xu

In the central nervous system (CNS), a large group of glial cells called astrocytes play important roles in both physiological and disease conditions. Astrocytes participate in the formation of neurovascular units and interact closely with other cells of the CNS, such as microglia and neurons. Stroke is a global disease with high mortality and disability rate, most of which are ischemic stroke. Significant strides in understanding astrocytes have been made over the past few decades. Astrocytes respond strongly to ischemic stroke through a process known as activation or reactivity. Given the important role played by reactive astrocytes (RAs) in different spatial and temporal aspects of ischemic stroke, there is a growing interest in the potential therapeutic role of astrocytes. Currently, interventions targeting astrocytes, such as mediating astrocyte polarization, reducing edema, regulating glial scar formation, and reprogramming astrocytes, have been proven in modulating the progression of ischemic stroke. The aforementioned potential interventions on astrocytes and the crosstalk between astrocytes and other cells of the CNS will be summarized in this review.

在中枢神经系统(CNS)中,一大群被称为星形胶质细胞的胶质细胞在生理和疾病状态下都发挥着重要作用。星形胶质细胞参与神经血管单元的形成,并与中枢神经系统的其他细胞(如小胶质细胞和神经元)密切互动。中风是一种全球性疾病,死亡率和致残率都很高,其中大部分是缺血性中风。过去几十年来,人们在了解星形胶质细胞方面取得了长足进步。星形胶质细胞对缺血性中风的强烈反应过程被称为激活或反应性。鉴于反应性星形胶质细胞(RA)在缺血性中风的不同空间和时间方面所起的重要作用,人们对星形胶质细胞的潜在治疗作用越来越感兴趣。目前,针对星形胶质细胞的干预措施,如介导星形胶质细胞极化、减轻水肿、调节胶质瘢痕的形成以及对星形胶质细胞进行重编程等,在调节缺血性卒中的进展方面已得到证实。本综述将总结上述对星形胶质细胞的潜在干预措施以及星形胶质细胞与中枢神经系统其他细胞之间的相互影响。
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引用次数: 0
Ribosomal protein SA is a common component of neuronal intranuclear inclusions in polyglutamine diseases and Marinesco bodies. 核糖体蛋白 SA 是多聚谷氨酰胺疾病和马林斯科体中神经元核内包涵体的常见成分。
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-02-01 Epub Date: 2023-06-21 DOI: 10.1111/neup.12927
Kaoru Yagita, Shoko Sadashima, Sachiko Koyama, Hideko Noguchi, Hideomi Hamasaki, Naokazu Sasagasako, Hiroyuki Honda

Neuronal intranuclear inclusions (NIIs) are common key structures in polyglutamine (polyQ) diseases such as Huntington disease (HD), spinocerebellar ataxia type 1 (SCA1), and SCA3. Marinesco bodies (MBs) of dopaminergic neurons in the substantia nigra are also intranuclear structures and are frequently seen in normal elderly people. Ribosomal dysfunction is closely related to two differential processes; therefore, we aimed to identify the pathological characteristics of ribosomal protein SA (RPSA), a ribosomal protein, in both states. To this end, we evaluated the autopsy findings in four patients with HD, two SCA3, and five normal elderly cases (NCs). Immunohistochemical studies demonstrated that both NIIs and MBs contain RPSA. In polyQ diseases, RPSA was co-localized with polyQ aggregations, and 3D-reconstructed images revealed their mosaic-like distribution. Assessments of the organization of RPSA and p62 in NIIs showed that RPSA was more localized toward the center than p62 and that this unique organization was more evident in the MBs. Immunoblotting of the temporal cortices revealed that the nuclear fraction of HD patients contained more RPSA than that of NCs. In conclusion, our study revealed that RPSA is a common component of both NIIs and MBs, indicating that a similar mechanism contributes to the formation of polyQ NIIs and MBs.

神经元核内包涵体(NII)是多谷氨酰胺(polyQ)疾病(如亨廷顿病(HD)、脊髓小脑共济失调 1 型(SCA1)和 SCA3)中常见的关键结构。黑质中多巴胺能神经元的马林斯科体(MBs)也是核内结构,在正常老年人中经常出现。核糖体功能障碍与这两种不同的过程密切相关;因此,我们旨在确定核糖体蛋白 SA(RPSA)在这两种状态下的病理特征。为此,我们对四名 HD 患者、两名 SCA3 患者和五名正常老年病例(NCs)的尸检结果进行了评估。免疫组化研究表明,NII 和 MB 均含有 RPSA。在多Q疾病中,RPSA与多Q聚集体共定位,三维重建图像显示了其马赛克样分布。通过评估RPSA和p62在NIIs中的组织结构,发现RPSA比p62更多地向中心定位,这种独特的组织结构在MBs中更为明显。颞叶皮层的免疫印迹显示,HD 患者的核部分比 NCs 中含有更多的 RPSA。总之,我们的研究发现,RPSA 是 NIIs 和 MBs 的共同成分,这表明多 Q NIIs 和 MBs 的形成有类似的机制。
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引用次数: 0
Prednisolone improves hippocampal regeneration after trimethyltin-induced neurodegeneration in association with prevention of T lymphocyte infiltration. 泼尼松龙能改善三甲基锡诱导的神经退行性病变后的海马再生,并能防止T淋巴细胞浸润。
IF 2.3 4区 医学 Q2 Medicine Pub Date : 2024-02-01 Epub Date: 2023-06-08 DOI: 10.1111/neup.12926
Masashi Sakurai, Miki Takenaka, Yuki Mitsui, Yusuke Sakai, Masahiro Morimoto

The endogenous regenerative capacity of the brain is quite weak; however, a regenerative reaction, the production of new neurons (neurogenesis), has been reported to occur in brain lesions. In addition, leukocytes are well known to infiltrate brain lesions. Therefore, leukocytes would also have a link with regenerative neurogenesis; however, their role has not been fully elucidated. In this study, we investigated leukocyte infiltration and its influence on brain tissue regeneration in a trimethyltin (TMT)-injected mouse model of hippocampal regeneration. Immunohistochemically, CD3-positive T lymphocytes were found in the hippocampal lesion of TMT-injected mice. Prednisolone (PSL) treatment inhibited T lymphocyte infiltration and increased neuronal nuclei (NeuN)-positive mature neurons and doublecortin (DCX)-positive immature neurons in the hippocampus. Investigation of bromodeoxyuridine (BrdU)-labeled newborn cells revealed the percentage of BrdU/NeuN- and BrdU/DCX-positive cells increased by PSL treatment. These results indicate that infiltrated T lymphocytes prevent brain tissue regeneration by inhibiting hippocampal neurogenesis.

大脑的内源性再生能力很弱,但有报道称,在大脑病变部位会出现再生反应,即产生新的神经元(神经发生)。此外,众所周知,白细胞会浸润脑损伤部位。因此,白细胞也与再生神经元的产生有关,但其作用尚未完全阐明。在本研究中,我们在注射三甲基锡(TMT)的小鼠海马再生模型中研究了白细胞浸润及其对脑组织再生的影响。免疫组化结果显示,在注射三甲基锡的小鼠海马病灶中发现了 CD3 阳性的 T 淋巴细胞。泼尼松龙(PSL)治疗抑制了T淋巴细胞的浸润,并增加了海马中神经元核(NeuN)阳性的成熟神经元和双皮质素(DCX)阳性的未成熟神经元。对溴脱氧尿苷(BrdU)标记的新生细胞进行的调查显示,PSL 处理后,BrdU/NeuN 和 BrdU/DCX 阳性细胞的百分比有所增加。这些结果表明,浸润的 T 淋巴细胞通过抑制海马神经发生来阻止脑组织再生。
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Neuropathology
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