JOURNAL OF NEUROPATHOLOGY & EXPERIMENTAL NEUROLOGY 是美国神经病理学家协会 (AANP) 的官方期刊。该杂志发表关于神经病理学和实验神经科学的同行评审研究、书评、信件和协会新闻，涵盖基础神经科学的广泛领域，重点是人类神经系统疾病。它由来自世界各地的神经病理学家、神经学家、神经外科医生、病理学家、精神病学家和基础神经科学家编写，并为它们编写。自 1942 年以来一直连续出版。

The Journal of Neuropathology and Experimental Neurology is the official journal of the American Association of Neuropathologists (AANP). This journal publishes peer-reviewed research, book reviews, letters, and association news related to neuropathology and experimental neuroscience, covering a wide range of areas in basic neuroscience with a focus on human neurological diseases. It has been continuously published since 1942, featuring contributions from neuropathologists, neurologists, neurosurgeons, pathologists, psychiatrists, and basic neuroscientists from around the world.

《Journal of Neuropathology and Experimental Neurology》是美国神经病理学家协会（AANP）的官方期刊。该期刊发表关于神经病理学和实验神经科学的同行评审研究、书评、信件和协会新闻，涵盖基础神经科学的广泛领域，特别关注人类神经系统疾病。自1942年以来，该期刊一直持续出版，作者包括来自世界各地的神经病理学家、神经学家、神经外科医生、病理学家、精神病学家和基础神经科学家。

Journal of Neuropathology and Experimental Neurology

Publication of the WHO Classification of Tumors of the Nervous System in 2000 represents the most recent combined effort of an international group of distinguished neuropathologists who have been focussing intensively on this issue since 1988. At that time, the late Dr. Klaus Zulch and Dr. William Fields convened a meeting in Houston to focus on three aspects that they thought required special attention since deliberations by a committee working under the sponsorship of the World Health Organization (WHO) had published their consensus document in 1979 (1).

The three areas of focus at the 1988 meeting in Houston, Texas included the concept of primitive neuroectodermal tumor and its relationship to medulloblastoma, grading of glial tumors and histo-biologic aspects of meningioma. Proceedings of this meeting were published and served as background studies for a second meeting of the WHO …

Lucy Balian Rorke

Journal of Neuropathology & Experimental Neurology

Commentary on the WHO Classification of Tumors of the Nervous System

The loss and degeneration of spinal cord motor neurons result in muscle denervation in spinal muscular atrophy (SMA), but whether there are primary pathogenetic abnormalities of muscle in SMA is not known. We previously detected increased DNA fragmentation and downregulation of Bcl-2 and Bcl-X(L) expression but no morphological changes in spinal motor neurons of SMA fetuses. Here, we performed histological and morphometric analysis of myotubes and assessed DNA fragmentation and Bcl-2/Bcl-X(L) expression in skeletal muscle from fetuses with type I SMA (at approximately 12 and 15 weeks' gestational ages, n = 4) and controls (at approximately 10-15 weeks' gestational ages, n = 7). Myotubes were smaller in the SMA than in control samples at all ages analyzed (p < 0.001) and were often arranged in clusters close to isolated and larger myotubes. Numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells in control and SMA fetuses were similar, and no differences in Bcl-2 or Bcl-X(L) immunostaining between control and SMA muscle were identified. Areas with smaller myotubes and the morphometric analysis suggested a delay in growth and maturation in SMA muscle. These results suggest that spinal motor neurons and skeletal muscle undergo different pathogenetic processes in SMA during development; they imply that muscle as well as motor neurons may be targets for early therapeutic intervention in SMA.

Rebeca Martínez-Hernández

Carolina Soler-Botija

Eva Also

Laura Alias

Lidia Caselles

Ignasi Gich

Sara Bernal

Eduardo F. Tizzano

The Developmental Pattern of Myotubes in Spinal Muscular Atrophy Indicates Prenatal Delay of Muscle Maturation

脊髓性肌萎缩中肌管的发育模式表明肌肉成熟存在产前延迟

Nicotinamide N-methyltransferase (NNMT) has been proposed as a link between the environmental and genetic factors of Parkinson disease (PD). Therefore, we explored the hypothesis that high levels of NNMT expression may predispose to the development of PD. Regions of high mRNA expression were shown in the spinal cord, medulla, and temporal lobe, with lowest expression in the cerebellum, subthalamic nucleus, and caudate nucleus. Using 2 NNMT antibodies, the protein was shown to be expressed in multipolar neurons in the temporal lobe, caudate nucleus, and spinal cord, granular neurons of the cerebellum, dopaminergic neurons in the substantia nigra, and in the axons of the third nerve. Expression of NNMT was compared in PD and non-PD control cerebella and caudate nucleus. PD tissue exhibited significantly increased levels of NNMT protein and activity. PD disease duration was inversely correlated with the level of expression in cerebellum. This is the first demonstration that patients with PD have higher levels of NNMT activity and protein in brain tissue than those without PD and that NNMT expression is associated with neurons that degenerate in PD.

Richard B. Parsons

Marie-Louise Smith

Adrian C. Williams

Rosemary H. Waring

David B. Ramsden

Expression of Nicotinamide N-Methyltransferase (E.C. 2.1.1.1) in the Parkinsonian Brain

帕金森病脑中烟酰胺N-甲基转移酶（E.C. 2.1.1.1）的表达

There are currently no standardized therapies for Parkinson disease (PD). Curcumin shows anti-amyloidogenic properties in vitro and may be a promising treatment for PD. We evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients to treated with curcumin. The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study. Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed a decrease of COMPASS-31 and NMSS scores, and a slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses. Multiple regression models showed a significant effect of curcumin supplementation in decreasing the worsening of the clinical parameters and p-syn load at after curcumin treatment. These data suggest that curcumin can cross the blood-brain barrier, that it is effective in ameliorating clinical parameters and that it shows a tendency to decrease skin p-syn accumulation in PD patients.

Vincenzo Donadio

Alex Incensi

Giovanni Rizzo

Enrico Fileccia

Francesco Ventruto

Antonella Riva

Domenico Tiso

Martino Recchia

Veria Vacchiano

Rossella Infante

Giovanna Petrangolini

Pietro Allegrini

Silvia Avino

Roberta Pantieri

Barbara Mostacci

Patrizia Avoni

Rocco Liguori

The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study

姜黄素对特发性帕金森病的影响：一项临床与皮肤活检研究

Abstract Hippocampal dentate gyral dysplasia is well-described in temporal lobe epilepsy and may be a risk factor for sudden, unexpected death in several populations: infants (sudden infant death syndrome [SIDS], sudden unexpected infant death [SUID]), toddlers (sudden unexpected death of a child [SUDC]), and epileptics (sudden unexpected death in epilepsy [SUDEP]). We examined reports and histopathological slides from autopsies performed at our institution from 2008 through 2016 to determine whether the presence or absence of any of the described forms of such dysplasias (duplications, hyperconvolutions, and granule cell dispersion, including bilamination), correlated with the causes of death. From well over 4000 autopsies, we identified 949 autopsies with a neuropathology examination by a neuropathologist. Of these, 205 cases (21.6%) had 1 or more of the described abnormalities of 1 or both dentate gyri; 87 (42.4%) of the individuals in this group of 205 autopsies had died suddenly and unexpectedly, including 29/90 (32.2%) cases of SUDEP, 17/31 (54.8%) cases of SUDC, and 51/104 (49.0%) cases of infants with SIDS or SUID. We conclude that these changes are readily recognizable by experienced neuropathologists and that because they are overrepresented in an autopsy population that died suddenly and unexpectedly, they may represent a risk factor for such outcomes.

Douglas C Miller

Kristen M Scheitler

Jeffery Holloway

C Christopher Stacy

Hippocampal dentate gyrus dysplasia and the risk of sudden unexpected death

海马齿状回发育不良与意外猝死风险

Abstract Intracranial aneurysms (IAs) affect 1%-5% of the public and are a major cause of subarachnoid hemorrhage. Currently, there is no medical treatment to prevent the progression or rupture of IAs. Recent studies have defined IA as a chronic inflammatory disease in which macrophages infiltrate intracranial arteries via the CCL2-CCR2 axis. The chemokine signal regulator FROUNT mediates this axis, and it can be inhibited by the anti-alcoholism drug disulfiram. Therefore, inhibition of macrophage infiltration by interfering with FROUNT using disulfiram may represent a strategy to prevent exacerbation of IAs. Here, effects of disulfiram were investigated in vitro and in an animal model of IAs. FROUNT expression was observed on infiltrated macrophages both in human IAs and in the rat IA model by immunohistochemistry. In vitro treatment with disulfiram suppressed CCL2-mediated migration of cultured rat macrophages in a transwell system. Disulfiram administered in a rat model of IAs inhibited both the initiation and the enlargement of IAs in a dose-dependent manner; this was accompanied by suppression of macrophage infiltration. These results suggest that pharmacological inhibition of the CCL2-CCR2-FROUNT signaling cascade could be a treatment of patients with IAs.

Isao Ono

Masahiko Itani

Akihiro Okada

Akitsugu Kawashima

Etsuko Toda

Yoshiki Arakawa

Yuya Terashima

Tomohiro Aoki

Potential of the pharmacological inhibition of CCL2-CCR2 axis via targeting FROUNT to prevent the initiation and the progression of intracranial aneurysms in rats

通过靶向FROUNT抑制CCL2-CCR2轴的药理学潜力，以预防大鼠颅内动脉瘤的形成和进展

Abstract High-grade infiltrating gliomas are highly aggressive and fatal brain tumors that present significant challenges for research and treatment due to their complex microenvironment and tissue structure. Recent discovery of tumor microtubes (TMs) has provided new insights into how high-grade gliomas develop in the brain and resist treatment. TMs are unique, ultra-long, and highly functional membrane protrusions that form multicellular networks and play crucial roles in glioma invasiveness, drug resistance, recurrence, and heterogeneity. This review focuses on the different roles that TMs play in glioma cell communication, material transport, and tumor cell behavior. Specifically, non-connecting TMs primarily promote glioma invasiveness, likely related to their role in enhancing cell motility. On the other hand, interconnecting TMs form functional and communication networks by connecting with surrounding astrocytes and neurons, thereby promoting glioma malignancy. We summarize the factors that influence the formation of TMs in gliomas and current strategies targeting TMs. As the understanding of TMs advances, we are closer to uncovering whether they might be the long-sought Achilles’ heel of treatment-resistant gliomas. By delving deeper into TMs research, we hope to develop more effective therapeutic strategies for patients with malignant gliomas.

Yunzhu Guo

Yangxin Li

Peng Su

Min Yan

Ming Wang

Shenjie Li

Wei Xiang

Ligang Chen

Wei Dong

Zhengjun Zhou

Jie Zhou

Tumor microtubes: A new potential therapeutic target for high-grade gliomas

肿瘤微管：高级别胶质瘤的新潜在治疗靶点

Abstract Cancer of unknown primary (CUP) constitutes between 2% and 5% of human malignancies and is among the most common causes of cancer death in the United States. Brain metastases are often the first clinical presentation of CUP; despite extensive pathological and imaging studies, 20%-45% of CUP are never assigned a primary site. DNA methylation array profiling is a reliable method for tumor classification but tumor-type-specific classifier development requires many reference samples. This is difficult to accomplish for CUP as many cases are never assigned a specific diagnosis. Recent studies identified subsets of methylation quantitative trait loci (mQTLs) unique to specific organs, which could help increase classifier accuracy while requiring fewer samples. We performed a retrospective genome-wide methylation analysis of 759 carcinoma samples from formalin-fixed paraffin-embedded tissue samples using Illumina EPIC array. Utilizing mQTL specific for breast, lung, ovarian/gynecologic, colon, kidney, or testis (BLOCKT) (185k total probes), we developed a deep learning-based methylation classifier that achieved 93.12% average accuracy and 93.04% average F1-score across a 10-fold validation for BLOCKT organs. Our findings indicate that our organ-based DNA methylation classifier can assist pathologists in identifying the site of origin, providing oncologists insight on a diagnosis to administer appropriate therapy, improving patient outcomes.

Adam Walker

Camila S Fang

Chanel Schroff

Jonathan Serrano

Varshini Vasudevaraja

Yiying Yang

Sarra Belakhoua

Arline Faustin

Christopher M William

David Zagzag

Sarah Chiang

Andres Martin Acosta

Misha Movahed-Ezazi

Kyung Park

Andre L Moreira

Farbod Darvishian

Kristyn Galbraith

Matija Snuderl

Deep learning-based classifier for carcinoma of unknown primary using methylation quantitative trait loci

基于深度学习的未知原发癌甲基化数量性状位点分类器

In situ hybridization (ISH) staining of bacterial 16S ribosomal RNA (rRNA) is an alternative to standard histological stains (eg, Gram, Warthin-Starry), and may improve the diagnosis of bacterial brain abscesses. To evaluate the utility of 16S rRNA ISH, a 10-year retrospective cohort was assembled from a large academic medical center. Results of histological stains, cultures, and 16S rRNA sequencing were extracted from reports, and new Gram and 16S rRNA ISH stains were performed. Histologically identifiable bacteria were present in 40/63 (63%) cases and 38/57 (67%) were associated with positive cultures. Overall, 16S rRNA ISH was positive in 18/63 (29%) cases, including 16/37 (43%) with positive Gram stains, 12/38 (32%) positive by culture, and 4/8 (50%) positive by sequencing. 16S rRNA ISH highlighted bacteria in 14/40 (35%) cases with Gram-positive organisms and 9/17 (53%) with Gram-negative organisms (including 6 polymicrobial cases). Compared to a composite gold standard of Gram stain and culture, the sensitivity and specificity of 16S rRNA ISH were 35% and 93%, respectively. While sensitivity is relatively low, 16S rRNA ISH may be useful for distinguishing real organisms from artifacts and for identifying brain abscess cases suitable for 16S rRNA sequencing.

William Mbongo

Alvaro C Laga

Isaac H Solomon

Detection of Gram-positive and Gram-negative bacteria in brain abscesses by 16S rRNA in situ hybridization

脑脓肿中革兰氏阳性菌和革兰氏阴性菌的16S rRNA原位杂交检测

Abbreviation	J Neuropathol Exp Neurol
Journal Impact	3.28
Quartiles(Global)	PATHOLOGY(Q2)

ISSN	0022-3069, 1554-6578
h-index	178

Publication Information	Publisher: Oxford University Press，Publishing cycle: Monthly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1942，Proportion of original research papers: 93.98%，Self Citation Rate:9.40%， Gold OA Rate: 19.42%
Average review cycle	网友分享经验：较慢,6-12周
Average recruitment ratio	网友分享经验：一般

Journal of Neuropathology and Experimental Neurology

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Commentary on the WHO Classification of Tumors of the Nervous System

The Developmental Pattern of Myotubes in Spinal Muscular Atrophy Indicates Prenatal Delay of Muscle Maturation

Expression of Nicotinamide N-Methyltransferase (E.C. 2.1.1.1) in the Parkinsonian Brain

The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study

Hippocampal dentate gyrus dysplasia and the risk of sudden unexpected death

Potential of the pharmacological inhibition of CCL2-CCR2 axis via targeting FROUNT to prevent the initiation and the progression of intracranial aneurysms in rats

Tumor microtubes: A new potential therapeutic target for high-grade gliomas

Deep learning-based classifier for carcinoma of unknown primary using methylation quantitative trait loci

Hippocampal dentate gyrus dysplasia and the risk of sudden unexpected death

Detection of Gram-positive and Gram-negative bacteria in brain abscesses by 16S rRNA in situ hybridization