Objective To analyze the disease spectrum and clinicopathological characteristics of central nervous system(CNS)diseases diagnosed based on pathological findings in Tibet. Methods We collected the data of all the cases with CNS lesions in Tibet Autonomous Region People's Hospital from January 2013 to December 2020.The clinicopathological features were analyzed via light microscopy,immunohistochemical staining,and special staining. Results A total of 383 CNS cases confirmed by pathological diagnosis were enrolled in this study,with a male-to-female ratio of 188∶195 and an average age of(40.03±17.39)years(0-74 years).Among them,127(33.2%)cases had non-neoplastic diseases,with a male-to-female ratio of 82∶45 and an average age of(31.99±19.29)years;256(66.8%)cases had neoplastic diseases,with a male-to-female ratio of 106∶150 and an average age of(44.01±14.87)years.The main non-neoplastic diseases were nervous system infectious diseases,cerebral vascular diseases,meningocele,cerebral cyst,and brain trauma.Among the infectious diseases,brain abscess,granulomatous inflammation,cysticercosis,and hydatidosis were common.The main neoplastic diseases included meningioma,pituitary adenoma,neuroepithelial tumor,schwannoma,metastatic tumor,and hemangioblastoma.The meningioma cases consisted of 95.4%(103/108)cases of grade Ⅰ,3.7%(4/108)cases of grade Ⅱ,and only 1(1/108,0.9%)case of grade Ⅲ.Among the neuroepithelial tumor cases,the top three were glioblastoma,grade Ⅲ diffuse glioma,and ependymoma. Conclusions There are diverse CNS diseases confirmed by pathological diagnosis in Tibet,among which non-neoplastic diseases account for 1/3 of all the cases.Infectious and vascular diseases are the most common non-neoplastic diseases in Tibet,and tuberculosis and parasitic infections are relatively common.The types and proportion of brain tumors in Tibet are different from those in other regions of China,and meningioma is the most common in Tibet,with higher proportion than neuroepithelial tumor.
Adolescent ; Adult ; Aged ; Brain Neoplasms/diagnosis* ; Central Nervous System Diseases/pathology* ; Child ; Child, Preschool ; Ependymoma ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Meningeal Neoplasms ; Middle Aged ; Retrospective Studies ; Tibet/epidemiology* ; Young Adult

BACKGROUND: Large-nerve fiber dysfunction, as assessed by vibration perception threshold (VPT) predicts risks of ulceration, amputation, and mortality in diabetes. Serum uric acid (UA) is closely associated with various metabolic disorders, especially diabetes. Thus, we sought to investigate the clinical relevance of UA to large-nerve fiber dysfunction, among patients with type 2 diabetes (T2D). METHODS: Medical records of consecutive patients with T2D who were admitted to Beijing Friendship Hospital Pinggu Campus between May 2014 and December 2016 were collected. Data for the 824 eligible patients included in the final analysis were extracted using a structured form. A VPT value ≥15 in either foot was defined as abnormal. We compared the clinical characteristics between patients with abnormal VPT and those with normal VPT (VPT value <15 in both feet) in the overall population and in gender subgroups. Logistic regression analysis was performed to explore the association of abnormal VPT with UA level. One-way analysis of variance was used to compare VPT values across four UA quartiles. RESULTS: UA levels were significantly lower in T2D patients with abnormal VPT than in those with normal VPT (294.5 ± 84.0 vs. 314.9 ± 92.8 μmol/L, P < 0.01), especially among male patients (311.7 ± 85.2 vs. 336.9 ± 89.6 μmol/L, P < 0.01). From the logistic regression analysis, hyperuricemia (males >420 μmol/L; females >360 μmol/L) was associated with a reduced risk of abnormal VPT (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.39-0.91; P < 0.05). This association was robust in male patients (OR, 0.43; 95% CI, 0.24-0.76; P < 0.01) but not in female patients (OR, 0.92; 95% CI, 0.47-1.82; P = 0.816), even after adjustment for confounding factors. For the younger male subgroup (age <65 years), VPT values decreased as the UA level increased (P for trend = 0.002), but this trend was not significant in older male subgroup (age ≥65 years; P for trend = 0.400). CONCLUSIONS Low serum UA levels showed a significant association with an increased risk of large-nerve fiber dysfunction in male patients with T2D, but not in female patients with T2D. In addition, in only the younger subgroup of male patients (<65 years), lower levels of UA also correlated with higher VPT values.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; blood ; pathology ; Female ; Humans ; Male ; Middle Aged ; Nerve Fibers ; pathology ; Peripheral Nervous System Diseases ; blood ; pathology ; Uric Acid ; blood ; Young Adult

In this review, combined post-mortem brain magnetic resonance imaging (MRI) and histology studies are highlighted, illustrating the relevance of translational approaches to define novel MRI signatures of neuropathological lesions in neuroinflammatory and neurodegenerative disorders. Initial studies combining post-mortem MRI and histology have validated various MRI sequences, assessing their sensitivity and specificity as diagnostic biomarkers in neurologic disease. More recent studies have focused on defining new radiological (bio)markers and implementing them in the clinical (research) setting. By combining neurological and neuroanatomical expertise with radiological development and pathological validation, a cycle emerges that allows for the discovery of novel MRI biomarkers to be implemented in vivo. Examples of this cycle are presented for multiple sclerosis, Alzheimer's disease, Parkinson's disease, and traumatic brain injury. Some applications have been shown to be successful, while others require further validation. In conclusion, there is much to explore with post-mortem MRI and histology studies, which can eventually be of high relevance for clinical practice.
Animals ; Brain ; diagnostic imaging ; pathology ; Humans ; Magnetic Resonance Imaging ; methods ; Nervous System Diseases ; diagnostic imaging ; pathology

OBJECTIVE: Astrocyte dysfunctions are related to several central nervous system (CNS) pathologies. Transcriptomic profiling of human mRNAs to investigate astrocyte functions may provide the basic molecular-biological data pertaining to the cellular activities of astrocytes. METHODS: Human Primary astrocytes (HPAs) and human neural stem cell line (HB1.F3) were used for differential digital gene analysis. In this study, a massively parallel sequencing platform, next-generation sequencing (NGS), was used to obtain the digital gene expression (DGE) data from HPAs. A comparative analysis of the DGE from HPA and HB1.F3 cells was performed. Sequencing was performed using NGS platform, and subsequently, bioinformatic analyses were implemented to reveal the identity of the pathways, relatively up- or down-regulated in HPA cells. RESULTS: The top, novel canonical pathways up-regulated in HPA cells than in the HB1.F3 cells were “Cyclins and cell cycle regulation,” “Integrin signaling,” “Regulation of eIF4 and p70S6K signaling,” “Wnt/β-catenin signaling,” “mTOR signaling,” “Aryl hydrocarbon receptor signaling,” “Hippo signaling,” “RhoA signaling,” “Signaling by Rho family GTPases,” and “Glioma signaling” pathways. The down-regulated pathways were “Cell cycle: G1/S checkpoint regulation,” “eIF2 signaling,” “Cell cycle: G2/M DNA damage checkpoint regulation,” “Telomerase signaling,” “RhoGDI signaling,” “NRF2-mediated oxidative stress response,” “ERK/MAPK signaling,” “ATM signaling,” “Pancreatic adenocarcinoma signaling,” “VEGF signaling,” and “Role of CHK proteins in cell cycle checkpoint control” pathways. CONCLUSION: This study would be a good reference to understand astrocyte functions at the molecular level, and to develop a diagnostic test, based on the DGE pattern of astrocytes, as a powerful, new clinical tool in many CNS diseases.
Adenocarcinoma ; Astrocytes ; Cell Cycle ; Cell Cycle Checkpoints ; Central Nervous System ; Central Nervous System Diseases ; Computational Biology ; Diagnostic Tests, Routine ; DNA Damage ; Gene Expression ; High-Throughput Nucleotide Sequencing ; Humans ; Neural Stem Cells ; Oxidative Stress ; Pathology ; Ribosomal Protein S6 Kinases, 70-kDa ; RNA, Messenger

BACKGROUND: Tauopathies, a class of neurodegenerative diseases that includes Alzheimer's disease (AD), are characterized by the deposition of neurofibrillary tangles composed of hyperphosphorylated tau protein in the human brain. As abnormal alterations in histone acetylation and methylation show a cause and effect relationship with AD, we investigated the role of several Jumonji domain-containing histone demethylase (JHDM) genes, which have yet to be studied in AD pathology. METHODS: To examine alterations of several JHDM genes in AD pathology, we performed bioinformatics analyses of JHDM gene expression profiles in brain tissue samples from deceased AD patients. Furthermore, to investigate the possible relationship between alterations in JHDM gene expression profiles and AD pathology in vivo, we examined whether tissue-specific downregulation of JHDM Drosophila homologs (kdm) can affect tauR406W-induced neurotoxicity using transgenic flies containing the UAS-Gal4 binary system. RESULTS: The expression levels of JHDM1A, JHDM2A/2B, and JHDM3A/3B were significantly higher in postmortem brain tissue from patients with AD than from non-demented controls, whereas JHDM1B mRNA levels were downregulated in the brains of patients with AD. Using transgenic flies, we revealed that knockdown of kdm2 (homolog to human JHDM1), kdm3 (homolog to human JHDM2), kdm4a (homolog to human JHDM3A), or kdm4b (homolog to human JHDM3B) genes in the eye ameliorated the tauR406W-engendered defects, resulting in less severe phenotypes. However, kdm4a knockdown in the central nervous system uniquely ameliorated tauR406W-induced locomotion defects by restoring heterochromatin. CONCLUSION: Our results suggest that downregulation of kdm4a expression may be a potential therapeutic target in AD.
Acetylation ; Alzheimer Disease ; Brain ; Central Nervous System ; Computational Biology ; Diptera ; Down-Regulation ; Drosophila melanogaster ; Drosophila ; Heterochromatin ; Histones ; Humans ; Locomotion ; Methylation ; Neurodegenerative Diseases ; Neurofibrillary Tangles ; Pathology ; Phenotype ; RNA, Messenger ; tau Proteins ; Tauopathies ; Transcriptome

Parkinson's disease (PD) is a common neurodegenerative disorder arising from an interplay between genetic and environmental risk factors. Studies have suggested that the pathological hallmarks of intraneuronal α-synuclein aggregations may start from the olfactory bulb and the enteric nervous system of the gut and later propagate to the brain via the olfactory tract and the vagus nerve. This hypothesis correlates well with clinical symptoms, such as constipation, that may develop up to 20 years before the onset of PD motor symptoms. Recent interest in the gut–brain axis has led to vigorous research into the gastrointestinal pathology and gut microbiota changes in patients with PD. In this review, we provide current clinical and pathological evidence of gut involvement in PD by summarizing the changes in gut microbiota composition and gut inflammation associated with its pathogenesis.
Brain ; Constipation ; Enteric Nervous System ; Gastrointestinal Microbiome ; Humans ; Inflammation ; Microbiota ; Neurodegenerative Diseases ; Olfactory Bulb ; Parkinson Disease ; Pathology ; Risk Factors ; Vagus Nerve

The aggregation of α-synuclein (α-syn) has been implicated in the pathogenesis of many neurodegenerative disorders, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Postmortem analyses of α-syn pathology, especially that of PD, have suggested that aggregates progressively spread from a few discrete locations to wider brain regions. The neuron-to-neuron propagation of α-syn has been suggested to be the underlying mechanism by which aggregates spread throughout the brain. Many cellular and animal models has been created to study cell-to-cell propagation. Recently, it has been shown that a single injection of preformed fibrils (PFFs) made of recombinant α-syn proteins into various tissues and organs of many different animal species results in widespread α-syn pathology in the central nervous system (CNS). These PFF models have been extensively used to study the mechanism by which aggregates spread throughout the brain. Here, we review what we have learned from PFF models, describe the nature of PFFs and the neuropathological features, neurophysiological characteristics, and behavioral outcomes of the models.
alpha-Synuclein ; Animals ; Brain ; Central Nervous System ; Dementia ; Lewy Bodies ; Models, Animal ; Multiple System Atrophy ; Neurodegenerative Diseases ; Parkinson Disease ; Pathology

Auditory brainstem responses (ABR) have been used as a powerful and the most common objective tool to evaluate hearing sensitivity and to diagnose the types of hearing loss and neurological disorders, through the auditory peripheral pathway to a central level of the brainstem, since 1971. Although bone-conduction (BC) ABR could be an alternative to air-conduction (AC) ABR, as the former overcomes some limitations of the latter, the majority of clinicians rarely utilize it due to a lack of knowledge and no routine test administration. This review presents the weaknesses of AC ABR that apply to all clinical population, and discusses the development of BC ABR. The optimal placements of bone oscillators to obtain favorable clinical outcomes in infants, children, and adults, and the appropriate stimuli for BC ABR are examined. While providing absolute thresholds and latencies of BC ABR based on previous studies compared to AC ABR, this review includes clinical data of infants and young children with both normal hearing in terms of maturation, and with pathology such as congenital external auditory canal atresia. We recommend the future clinical application of BC ABR for candidacy as well as for patients with BC hearing implants.
Adult ; Brain Stem ; Child ; Ear Canal ; Evoked Potentials, Auditory, Brain Stem ; Hearing ; Hearing Loss ; Humans ; Infant ; Nervous System Diseases ; Pathology

Taurine is an abundant, β-amino acid with diverse cytoprotective activity. In some species, taurine is an essential nutrient but in man it is considered a semi-essential nutrient, although cells lacking taurine show major pathology. These findings have spurred interest in the potential use of taurine as a therapeutic agent. The discovery that taurine is an effective therapy against congestive heart failure led to the study of taurine as a therapeutic agent against other disease conditions. Today, taurine has been approved for the treatment of congestive heart failure in Japan and shows promise in the treatment of several other diseases. The present review summarizes studies supporting a role of taurine in the treatment of diseases of muscle, the central nervous system, and the cardiovascular system. In addition, taurine is extremely effective in the treatment of the mitochondrial disease, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and offers a new approach for the treatment of metabolic diseases, such as diabetes, and inflammatory diseases, such as arthritis. The review also addresses the functions of taurine (regulation of antioxidation, energy metabolism, gene expression, ER stress, neuromodulation, quality control and calcium homeostasis) underlying these therapeutic actions.
Acidosis, Lactic ; Arthritis ; Brain Diseases ; Calcium ; Cardiovascular System ; Central Nervous System ; Cytoprotection ; Energy Metabolism ; Gene Expression ; Heart Failure ; Japan ; MELAS Syndrome ; Metabolic Diseases ; Mitochondrial Diseases ; Neurodegenerative Diseases ; Pathology ; Quality Control ; Taurine*

Understanding the underlying mechanisms of memory formation and maintenance has been a major goal in the field of neuroscience. Memory formation and maintenance are tightly controlled complex processes. Among the various processes occurring at different levels, gene expression regulation is especially crucial for proper memory processing, as some genes need to be activated while some genes must be suppressed. Epigenetic regulation of the genome involves processes such as DNA methylation and histone post-translational modifications. These processes edit genomic properties or the interactions between the genome and histone cores. They then induce structural changes in the chromatin and lead to transcriptional changes of different genes. Recent studies have focused on the concept of chromatin remodeling, which consists of 3D structural changes in chromatin in relation to gene regulation, and is an important process in learning and memory. In this review, we will introduce three major epigenetic processes involved in memory regulation: DNA methylation, histone methylation and histone acetylation. We will also discuss general mechanisms of long-term memory storage and relate the epigenetic control of learning and memory to chromatin remodeling. Finally, we will discuss how epigenetic mechanisms can contribute to the pathologies of neurological disorders and cause memory-related symptoms.
Acetylation ; Chromatin Assembly and Disassembly* ; Chromatin* ; DNA Methylation ; Epigenesis, Genetic ; Epigenomics* ; Gene Expression Regulation ; Genome ; Histones ; Learning* ; Memory* ; Memory, Long-Term ; Methylation ; Nervous System Diseases ; Neurosciences ; Pathology ; Protein Processing, Post-Translational