Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43.849
Filtrar
1.
Sensors (Basel) ; 23(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36679805

RESUMO

The reliable monitoring of the depth of anesthesia (DoA) is essential to control the anesthesia procedure. Electroencephalography (EEG) has been widely used to estimate DoA since EEG could reflect the effect of anesthetic drugs on the central nervous system (CNS). In this study, we propose that a deep learning model consisting mainly of a deep residual shrinkage network (DRSN) and a 1 × 1 convolution network could estimate DoA in terms of patient state index (PSI) values. First, we preprocessed the four raw channels of EEG signals to remove electrical noise and other physiological signals. The proposed model then takes the preprocessed EEG signals as inputs to predict PSI values. Then we extracted 14 features from the preprocessed EEG signals and implemented three conventional feature-based models as comparisons. A dataset of 18 patients was used to evaluate the models' performances. The results of the five-fold cross-validation show that there is a relatively high similarity between the ground-truth PSI values and the predicted PSI values of our proposed model, which outperforms the conventional models, and further, that the Spearman's rank correlation coefficient is 0.9344. In addition, an ablation experiment was conducted to demonstrate the effectiveness of the soft-thresholding module for EEG-signal processing, and a cross-subject validation was implemented to illustrate the robustness of the proposed method. In summary, the procedure is not merely feasible for estimating DoA by mimicking PSI values but also inspired us to develop a precise DoA-estimation system with more convincing assessments of anesthetization levels.


Assuntos
Anestesia , Humanos , Encéfalo/fisiologia , Processamento de Sinais Assistido por Computador , Eletroencefalografia/métodos , Sistema Nervoso Central
2.
Artigo em Inglês | MEDLINE | ID: mdl-36657993

RESUMO

BACKGROUND AND OBJECTIVES: Anti-CD20 monoclonal antibody (mAb) B-cell depletion is a remarkably successful multiple sclerosis (MS) treatment. Chimeric antigen receptor (CAR)-T cells, which target antigens in a non-major histocompatibility complex (MHC)-restricted manner, can penetrate tissues more thoroughly than mAbs. However, a previous study indicated that anti-CD19 CAR-T cells can paradoxically exacerbate experimental autoimmune encephalomyelitis (EAE) disease. We tested anti-CD19 CAR-T cells in a B-cell-dependent EAE model that is responsive to anti-CD20 B-cell depletion similar to the clinical benefit of anti-CD20 mAb treatment in MS. METHODS: Anti-CD19 CAR-T cells or control cells that overexpressed green fluorescent protein were transferred into C57BL/6 mice pretreated with cyclophosphamide (Cy). Mice were immunized with recombinant human (rh) myelin oligodendrocyte protein (MOG), which causes EAE in a B-cell-dependent manner. Mice were evaluated for B-cell depletion, clinical and histologic signs of EAE, and immune modulation. RESULTS: Clinical scores and lymphocyte infiltration were reduced in mice treated with either anti-CD19 CAR-T cells with Cy or control cells with Cy, but not with Cy alone. B-cell depletion was observed in peripheral lymphoid tissue and in the CNS of mice treated with anti-CD19 CAR-T cells with Cy pretreatment. Th1 or Th17 populations did not differ in anti-CD19 CAR-T cell, control cell-treated animals, or Cy alone. DISCUSSION: In contrast to previous data showing that anti-CD19 CAR-T cell treatment exacerbated EAE, we observed that anti-CD19 CAR-T cells ameliorated EAE. In addition, anti-CD19 CAR-T cells thoroughly depleted B cells in peripheral tissues and in the CNS. However, the clinical benefit occurred independently of antigen specificity or B-cell depletion.


Assuntos
Encefalomielite Autoimune Experimental , Imunoterapia Adotiva , Animais , Humanos , Camundongos , Anticorpos Monoclonais , Antígenos CD19 , Autoimunidade , Sistema Nervoso Central , Encefalomielite Autoimune Experimental/tratamento farmacológico , Camundongos Endogâmicos C57BL , Esclerose Múltipla/tratamento farmacológico , Glicoproteína Mielina-Oligodendrócito , Linfócitos T , Linfócitos B
3.
Ann Transplant ; 28: e938467, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36593744

RESUMO

BACKGROUND Myeloablative chemotherapy supported by autologous stem cell transplantation (ASCT) is an option for primary central nervous system lymphoma (PCNSL) in both the relapse setting and as postremission consolidation, but the level of evidence in this field is still low. MATERIAL AND METHODS We retrospectively analyzed 47 HIV-negative PCNSL patients from 2010 to 2021. To assess the outcomes in patients undergoing ASCT. RESULTS Of the 47 patients, the median age was 51 (range, 21-77) years, and 28 (59.6%) were male. After induction, 33 (70.2%) patients achieved complete remission, and 6 (12.8%) patients achieved partial remission. At a median follow-up of 21.4 months (95% CI 8.86-33.95), the median progression-free survival (PFS) was 23.3 months (95% CI 14.87-31.73), and the 4-year PFS rate was 14.6%. The median overall survival (OS) time was 62.4 months (95% CI 41.93-82.87), and the 4-year OS rate was 71.5%. Among 20 patients who received ASCT (10 consolidation, 10 salvage), the 4-year PFS and 4-year OS rates were 57.3% and 71.2%, respectively. In the multivariate analysis, ASCT therapy (hazard ratio [HR] 0.16, P=0.016) and early remission (HR 0.12, p=0.003) were found to be independent prognostic factors for a longer PFS. Two treatment-related deaths occurred in patients with multiple relapses before ASCT. Pancytopenia and diarrhea were the most common adverse events. CONCLUSIONS ASCT offers potential long-term PFS with good tolerability for patients with PCNSL. Our retrospective cohort adds to the currently available literature and identifies disease status after induction as a significant factor affecting survival.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Transplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva , Linfoma/cirurgia , Sistema Nervoso Central , Transplante de Células-Tronco
4.
Neurosurg Rev ; 46(1): 37, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36645525

RESUMO

The role of surgery in the management of primary central nervous system lymphomas (PCNSL) is currently confined to diagnosis. However, over recent years, an increasing number of papers have suggested a possible positive prognostic impact of surgery in selected cases. The present work aims to perform a meta-analysis of the available literature evidence. A meta-analysis with meta-regression on the role of surgical resection compared to biopsy in the management of PCNSL was conducted according to the PRISMA statement, searching MEDLINE via PubMed and Embase. The random effect model was used. The quality of evidence was assessed using the GRADE framework. After screening 1395 records, we included 11 papers in our analysis. Patients who underwent surgical resection harbored superficial and single-lesion tumors. At 1-, 2-, and 5-year follow-up, progression-free survival did not differ between the two groups, while overall survival favored resection, even if in a non-significant fashion. Meta-regression analysis showed that the overall survival rate at 2 years, but not at 1 or 5 years, was significantly influenced by tumor location. There were no differences in terms of age, sex, Karnofsky performance status, adjuvant therapy, or procedure-related complications. Overall, the quality of evidence is low. The results of the present meta-analysis do not change the current standard of care for PCNSL. However, surgery could be non-inferior to biopsy with an acceptable risk profile in selected patients harboring single and superficial lesions. The low quality of evidence prompts future randomized studies.


Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Linfoma , Humanos , Biópsia , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/cirurgia , Neoplasias Encefálicas/cirurgia , Linfoma/diagnóstico , Linfoma/cirurgia , Sistema Nervoso Central
5.
Viruses ; 15(1)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36680268

RESUMO

The cessation of measles virus (MeV) vaccination in more than 40 countries as a consequence of the COVID-19 pandemic is expected to significantly increase deaths due to measles. MeV can infect the central nervous system (CNS) and lead to lethal encephalitis. Substantial part of virus sequences recovered from patients' brain were mutated in the matrix and/or the fusion protein (F). Mutations of the heptad repeat domain located in the C terminal (HRC) part of the F protein were often observed and were associated to hyperfusogenicity. These mutations promote brain invasion as a hallmark of neuroadaptation. Wild-type F allows entry into the brain, followed by limited spreading compared with the massive invasion observed for hyperfusogenic MeV. Taking advantage of our ex vivo models of hamster organotypic brain cultures, we investigated how the hyperfusogenic mutations in the F HRC domain modulate virus distribution in CNS cells. In this study, we also identified the dependence of neural cells susceptibility on both their activation state and destabilization of the virus F protein. Type I interferon (IFN-I) impaired mainly astrocytes and microglial cells permissiveness contrarily to neurons, opening a new way of consideration on the development of treatments against viral encephalitis.


Assuntos
Sistema Nervoso Central , Vírus do Sarampo , Sarampo , Animais , Cricetinae , Humanos , Encéfalo , Sistema Nervoso Central/virologia , Interferons/metabolismo , Vírus do Sarampo/fisiologia , Proteínas Virais de Fusão/genética
6.
Funct Integr Genomics ; 23(1): 45, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36683116

RESUMO

Recent studies have confirmed the direct role of vitamin B12 (VitB12) in the central nervous system (CNS) homeostasis; nevertheless, the detailed mechanisms are poorly understood. By analyzing RNA-Seq and microarray datasets obtained from databanks, this study aims to identify possible basic mechanisms, related to the brain, involved in altering the gene expression under VitB12 deficiency mimicking conditions. The database inquiry returned datasets generated from distinctly heterogeneous experimental sets and considering the quality and relevance requirements, two datasets from mouse and one from rat models were selected. The analyses of individual datasets highlighted a change in ribosomal gene expression in VitB12 deficiency mimicking conditions within each system. Specifically, a divergent regulation was observed depending on the animal model: mice showed a down regulation of the ribosomal gene expression, while rats an upregulation. Interestingly, E2f1 was significantly upregulated under VitB12 deficiency mimicking conditions in the animal models, with a greater upregulation in rats. The rat model also revealed putative E2F1 Transcription Factor Binding Sites (TFBSs) in the promoter of the differently regulated genes involved in ribosomal gene expression. This suggested the possibility that E2F1, being greater expressed in rats, could activate the ribosomal genes having E2F1 TFBSs, thus giving a plausible explication to the divergent regulation observed in animal models. Despite the great diversity of the experimental sets used to generate the datasets considered, a common alteration of the ribosomes exists, thereby indicating a possible basic and conserved response to VitB12 deficiency. Moreover, these findings could provide new insights on E2F1 and its association with CNS homeostasis and VitB12 deficiency.


Assuntos
Deficiência de Vitamina B 12 , Vitamina B 12 , Ratos , Animais , Camundongos , Vitamina B 12/genética , Vitamina B 12/metabolismo , Deficiência de Vitamina B 12/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Sistema Nervoso Central/metabolismo , Expressão Gênica
7.
Biomolecules ; 13(1)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36671524

RESUMO

Glutamate is the major excitatory neurotransmitter in the central nervous system, and there is evidence that Group-I metabotropic glutamate receptors (mGlu1 and mGlu5) have established roles in excitatory neurotransmission and synaptic plasticity. While glutamate is abundantly present in the gut, it plays a smaller role in neurotransmission in the enteric nervous system. In this study, we examined the roles of Group-I mGlu receptors in gastrointestinal function. We investigated the expression of Grm1 (mGlu1) and Grm5 (mGlu5) in the mouse myenteric plexus using RNAscope in situ hybridization. Live calcium imaging and motility analysis were performed on ex vivo preparations of the mouse colon. mGlu5 was found to play a role in excitatory enteric neurotransmission, as electrically-evoked calcium transients were sensitive to the mGlu5 antagonist MPEP. However, inhibition of mGlu5 activity did not affect colonic motor complexes (CMCs). Instead, inhibition of mGlu1 using BAY 36-7620 reduced CMC frequency but did not affect enteric neurotransmission. These data highlight complex roles for Group-I mGlu receptors in myenteric neuron activity and colonic function.


Assuntos
Cálcio , Sistema Nervoso Central , Camundongos , Animais , Cálcio/farmacologia , Sistema Nervoso Central/metabolismo , Neurônios/metabolismo , Ácido Glutâmico/metabolismo , Transmissão Sináptica
8.
Int J Mol Sci ; 24(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36674852

RESUMO

Neurodegenerative diseases (NDs) are a major cause of disability and are related to brain development. The neurological signs of brain lesions can vary from mild clinical shortfalls to more delicate and severe neurological/behavioral symptoms and learning disabilities, which are progressive. In this paper, we have tried to summarize a collective view of various NDs and their possible therapeutic outcomes. These diseases often occur as a consequence of the misfolding of proteins post-translation, as well as the dysfunctional trafficking of proteins. In the treatment of neurological disorders, a challenging hurdle to cross regarding drug delivery is the blood-brain barrier (BBB). The BBB plays a unique role in maintaining the homeostasis of the central nervous system (CNS) by exchanging components between the circulations and shielding the brain from neurotoxic pathogens and detrimental compounds. Here, we outline the current knowledge about BBB deterioration in the evolving brain, its origin, and therapeutic interventions. Additionally, we summarize the physiological scenarios of the BBB and its role in various cerebrovascular diseases. Overall, this information provides a detailed account of BBB functioning and the development of relevant treatments for neurological disorders. This paper will definitely help readers working in the field of neurological scientific communities.


Assuntos
Doenças do Sistema Nervoso , Humanos , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Encéfalo/metabolismo , Barreira Hematoencefálica/metabolismo , Sistema Nervoso Central , Sistemas de Liberação de Medicamentos
9.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36675073

RESUMO

The purpose of this review is to attempt to outline the potential role of fluoride in the pathogenesis of brain tumours, including glioblastoma (GBM). In this paper, we show for the first time that fluoride can potentially affect the generally accepted signalling pathways implicated in the formation and clinical course of GBM. Fluorine compounds easily cross the blood-brain barrier. Enhanced oxidative stress, disruption of multiple cellular pathways, and microglial activation are just a few examples of recent reports on the role of fluoride in the central nervous system (CNS). We sought to present the key mechanisms underlying the development and invasiveness of GBM, as well as evidence on the current state of knowledge about the pleiotropic, direct, or indirect involvement of fluoride in the regulation of these mechanisms in various tissues, including neural and tumour tissue. The effects of fluoride on the human body are still a matter of controversy. However, given the growing incidence of brain tumours, especially in children, and numerous reports on the effects of fluoride on the CNS, it is worth taking a closer look at these mechanisms in the context of brain tumours, including gliomas.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Criança , Humanos , Fluoretos/metabolismo , Sistema Nervoso Central/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Barreira Hematoencefálica/metabolismo
10.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36675113

RESUMO

Both astrocytic and microglial functions have been extensively investigated in healthy subjects and neurodegenerative diseases. For astrocytes, not only various sub-types were identified but phagocytic activity was also clarified recently and is making dramatic progress. In this review paper, we mostly focus on the functional role of astrocytes in the extracellular matrix and on interactions between reactive astrocytes and reactive microglia in normal states and in neurodegenerative diseases, because the authors feel it is necessary to elucidate the mechanisms among activated glial cells in the pathology of neurological diseases in order to pave the way for drug discovery. Finally, we will review cyclic phosphatidic acid (cPA), a naturally occurring phospholipid mediator that induces a variety of biological activities in the brain both in vivo and in vitro. We propose that cPA may serve as a novel therapeutic molecule for the treatment of brain injury and neuroinflammation.


Assuntos
Microglia , Doenças Neurodegenerativas , Humanos , Microglia/patologia , Astrócitos/patologia , Doenças Neurodegenerativas/patologia , Sistema Nervoso Central , Neuroglia , Ácidos Fosfatídicos
11.
Neural Plast ; 2023: 4637073, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36644710

RESUMO

CX3CR1 is a G protein-coupled receptor that is expressed exclusively by microglia within the brain parenchyma. The only known physiological CX3CR1 ligand is the chemokine fractalkine (FKN), which is constitutively expressed in neuronal cell membranes and tonically released by them. Through its key role in microglia-neuron communication, the FKN/CX3CR1 axis regulates microglial state, neuronal survival, synaptic plasticity, and a variety of synaptic functions, as well as neuronal excitability via cytokine release modulation, chemotaxis, and phagocytosis. Thus, the absence of CX3CR1 or any failure in the FKN/CX3CR1 axis has been linked to alterations in different brain functions, including changes in synaptic and network plasticity in structures such as the hippocampus, cortex, brainstem, and spinal cord. Since synaptic plasticity is a basic phenomenon in neural circuit integration and adjustment, here, we will review its modulation by the FKN/CX3CR1 axis in diverse brain circuits and its impact on brain function and adaptation in health and disease.


Assuntos
Sistema Nervoso Central , Quimiocina CX3CL1 , Quimiocina CX3CL1/metabolismo , Receptor 1 de Quimiocina CX3C/metabolismo , Microglia/metabolismo , Medula Espinal/metabolismo
12.
PLoS Biol ; 21(1): e3001958, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36603052

RESUMO

Accumulating observations suggest that peripheral somatosensory ganglia may regulate nociceptive transmission, yet direct evidence is sparse. Here, in experiments on rats and mice, we show that the peripheral afferent nociceptive information undergoes dynamic filtering within the dorsal root ganglion (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using synchronous in vivo electrophysiological recordings from the peripheral and central processes of sensory neurons (in the spinal nerve and dorsal root), ganglionic transplantation of GABAergic progenitor cells, and optogenetics, we demonstrate existence of tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically induced GABA release within DRG from the transplanted GABAergic cells enhanced filtering and alleviated hypersensitivity to noxious stimulation produced by chronic inflammation and neuropathic injury in vivo. These findings support "gating" of pain information by DRGs and suggest new therapeutic approaches for pain relief.


Assuntos
Gânglios Espinais , Nociceptividade , Ratos , Camundongos , Animais , Ratos Sprague-Dawley , Gânglios Espinais/fisiologia , Sistema Nervoso Central , Dor , Ácido gama-Aminobutírico
13.
Nat Commun ; 14(1): 218, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639365

RESUMO

Familial dysautonomia (FD) is a rare genetic neurologic disorder caused by impaired neuronal development and progressive degeneration of both the peripheral and central nervous systems. FD is monogenic, with >99.4% of patients sharing an identical point mutation in the elongator acetyltransferase complex subunit 1 (ELP1) gene, providing a relatively simple genetic background in which to identify modifiable factors that influence pathology. Gastrointestinal symptoms and metabolic deficits are common among FD patients, which supports the hypothesis that the gut microbiome and metabolome are altered and dysfunctional compared to healthy individuals. Here we show significant differences in gut microbiome composition (16 S rRNA gene sequencing of stool samples) and NMR-based stool and serum metabolomes between a cohort of FD patients (~14% of patients worldwide) and their cohabitating, healthy relatives. We show that key observations in human subjects are recapitulated in a neuron-specific Elp1-deficient mouse model, and that cohousing mutant and littermate control mice ameliorates gut microbiome dysbiosis, improves deficits in gut transit, and reduces disease severity. Our results provide evidence that neurologic deficits in FD alter the structure and function of the gut microbiome, which shifts overall host metabolism to perpetuate further neurodegeneration.


Assuntos
Disautonomia Familiar , Microbioma Gastrointestinal , Humanos , Camundongos , Animais , Disautonomia Familiar/genética , Disbiose/metabolismo , Neurônios/metabolismo , Sistema Nervoso Central/metabolismo
14.
Commun Biol ; 6(1): 40, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639529

RESUMO

Astrocytes are resident glial cells of the central nervous system (CNS) that play complex and heterogeneous roles in brain development, homeostasis and disease. Since their vast involvement in health and disease is becoming increasingly recognized, suitable and reliable tools for studying these cells in vivo and in vitro are of utmost importance. One of the key challenges hereby is to adequately mimic their context-dependent in vivo phenotypes and functions in vitro. To better understand the spectrum of astrocytic variations in defined settings we performed a side-by-side-comparison of murine embryonic stem cell (ESC)-derived astrocytes as well as primary neonatal and adult astrocytes, revealing major differences on a functional and transcriptomic level, specifically on proliferation, migration, calcium signaling and cilium activity. Our results highlight the need to carefully consider the choice of astrocyte origin and phenotype with respect to age, isolation and culture protocols based on the respective biological question.


Assuntos
Astrócitos , Neuroglia , Animais , Camundongos , Astrócitos/fisiologia , Diferenciação Celular , Sistema Nervoso Central , Células-Tronco Embrionárias
15.
J Natl Compr Canc Netw ; 21(1): 12-20, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36634606

RESUMO

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2-3 oligodendroglioma [1p19q codeleted, IDH-mutant], WHO grade 2-4 IDH-mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non-AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding molecular profiling of gliomas.


Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Adulto , Humanos , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Sistema Nervoso Central , Mutação
16.
Subcell Biochem ; 102: 379-413, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36600141

RESUMO

Serotonin or 5-hydroxytryptamine (5-HT) is an important neurotransmitter in the central nervous system and the periphery. Most 5-HT (~99%) is found in the periphery where it regulates the function of the gastrointestinal (GI) tract and is an important regulator of platelet aggregation. However, the remaining 1% that is found in the central nervous system (CNS) can regulate a range of physiological processes such as learning and memory formation, mood, food intake, sleep, temperature and pain perception. More recent work on the CNS of invertebrate model systems has shown that 5-HT can directly regulate lifespan.This chapter will focus on detailing how CNS 5-HT signalling is altered with increasing age and the potential consequences this has on its ability to regulate lifespan.


Assuntos
Longevidade , Serotonina , Sistema Nervoso Central , Transdução de Sinais
17.
Zhonghua Bing Li Xue Za Zhi ; 52(1): 37-42, 2023 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-36617904

RESUMO

Objective: To study the clinicopathological characteristics, and further understand primary central nervous system T-cell lymphoma (PCNSTCL) in children and adolescents. Methods: Five cases of PCNSTCL in children and adolescents were collected from December 2016 to December 2021 at the First Affiliated Hospital of Zhengzhou University. The clinicopathological characteristics, immunophenotypic, and molecular pathologic features were analyzed, and relevant literatures reviewed. Results: There were two male and three female patients with a median age of 14 years (range 11 to 18 years). There were two peripheral T-cell lymphomas, not otherwise specified, two anaplastic large cell lymphoma, ALK-positive and one NK/T cell lymphoma. Pathologically, the tumor cells showed a variable histomorphologic spectrum, including small, medium and large cells with diffuse growth pattern and perivascular accentuation. Immunohistochemistry and in situ hybridization showed CD3 expression in four cases, and CD3 was lost in one case. CD5 expression was lost in four cases and retained in one case. ALK and CD30 were expressed in two cases. One tumor expressed CD56 and Epstein-Barr virus-encoded RNA. All cases showed a cytotoxic phenotype with expression of TIA1 and granzyme B. Three cases had a high Ki-67 index (>50%). T-cell receptor (TCR) gene rearrangement was clonal in two cases. Conclusions: PCNSTCL is rare, especially in children and adolescents. The morphology of PCNSTCL is diverse. Immunohistochemistry and TCR gene rearrangement play important roles in the diagnosis.


Assuntos
Neoplasias do Sistema Nervoso Central , Infecções por Vírus Epstein-Barr , Linfoma de Células T Periférico , Linfoma de Células T , Feminino , Humanos , Masculino , Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Herpesvirus Humano 4 , Linfoma de Células T/genética , Linfoma de Células T/patologia , Linfoma de Células T Periférico/genética , Receptores Proteína Tirosina Quinases/genética , Receptores de Antígenos de Linfócitos T , Criança , Adolescente
18.
J Clin Invest ; 133(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36594466

RESUMO

Glioblastoma (GBM) is the most aggressive tumor in the central nervous system and contains a highly immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages and microglia (TAMs) are a dominant population of immune cells in the GBM TME that contribute to most GBM hallmarks, including immunosuppression. The understanding of TAMs in GBM has been limited by the lack of powerful tools to characterize them. However, recent progress on single-cell technologies offers an opportunity to precisely characterize TAMs at the single-cell level and identify new TAM subpopulations with specific tumor-modulatory functions in GBM. In this Review, we discuss TAM heterogeneity and plasticity in the TME and summarize current TAM-targeted therapeutic potential in GBM. We anticipate that the use of single-cell technologies followed by functional studies will accelerate the development of novel and effective TAM-targeted therapeutics for GBM patients.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Microglia/patologia , Glioblastoma/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Macrófagos/patologia , Sistema Nervoso Central/patologia , Microambiente Tumoral
19.
Proc Natl Acad Sci U S A ; 120(4): e2209964120, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36669111

RESUMO

Sonic hedgehog signaling regulates processes of embryonic development across multiple tissues, yet factors regulating context-specific Shh signaling remain poorly understood. Exome sequencing of families with polymicrogyria (disordered cortical folding) revealed multiple individuals with biallelic deleterious variants in TMEM161B, which encodes a multi-pass transmembrane protein of unknown function. Tmem161b null mice demonstrated holoprosencephaly, craniofacial midline defects, eye defects, and spinal cord patterning changes consistent with impaired Shh signaling, but were without limb defects, suggesting a CNS-specific role of Tmem161b. Tmem161b depletion impaired the response to Smoothened activation in vitro and disrupted cortical histogenesis in vivo in both mouse and ferret models, including leading to abnormal gyration in the ferret model. Tmem161b localizes non-exclusively to the primary cilium, and scanning electron microscopy revealed shortened, dysmorphic, and ballooned ventricular zone cilia in the Tmem161b null mouse, suggesting that the Shh-related phenotypes may reflect ciliary dysfunction. Our data identify TMEM161B as a regulator of cerebral cortical gyration, as involved in primary ciliary structure, as a regulator of Shh signaling, and further implicate Shh signaling in human gyral development.


Assuntos
Furões , Proteínas Hedgehog , Animais , Feminino , Humanos , Camundongos , Gravidez , Sistema Nervoso Central/metabolismo , Cílios/genética , Cílios/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Camundongos Knockout , Transdução de Sinais
20.
J Nanobiotechnology ; 21(1): 32, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36707835

RESUMO

Although some tumor has become a curable disease for many patients, involvement of the central nervous system (CNS) is still a major concern. The blood-brain barrier (BBB), a special structure in the CNS, protects the brain from bloodborne pathogens via its excellent barrier properties and hinders new drug development for brain tumor. Recent breakthroughs in nanotechnology have resulted in various nanovehicless (NPs) as drug carriers to cross the BBB by different strategys. Here, the complex compositions and special characteristics of causes of brain tumor formation and BBB are elucidated exhaustively. Additionally, versatile drug nanovehicles with their recent applications and their pathways on different drug delivery strategies to overcome the BBB obstacle for anti-brain tumor are briefly discussed. Customizing nanoparticles for brain tumor treatments is proposed to improve the efficacy of brain tumor treatments via drug delivery from the gut to the brain. This review provides a broad perspective on customizing delivery nano-vehicles characteristics facilitate drug distribution across the brain and pave the way for the creation of innovative nanotechnology-based nanomaterials for brain tumor treatments.


Assuntos
Neoplasias Encefálicas , Nanopartículas , Humanos , Encéfalo/fisiologia , Barreira Hematoencefálica/metabolismo , Sistema Nervoso Central/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...