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1.
Brain Nerve ; 73(10): 1067-1074, 2021 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-34615743

RESUMO

What are desirable roles of general neurologists in the diagnosis and treatment of primary central nervous system lymphoma (PCNSL)? These issues were discussed 7 years back in the special feature articles of this journal. In the last 7 years genome analyses using liquid biopsy specimens have progressed and are becoming popular in the management of PCNSL, thereby enabling neurosurgeons to avoid invasive brain biopsy. The role of general neurologists in this country is not to be directly engaged in the PCNSL management, but to make an early diagnosis of PCNSL and to refer patients with PCNSL to specialists for a combination of chemotherapy and irradiation therapy.


Assuntos
Linfoma , Neurologistas , Sistema Nervoso Central , Humanos , Linfoma/diagnóstico , Linfoma/terapia
2.
Brain Nerve ; 73(10): 1079-1086, 2021 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-34615745

RESUMO

Primary central nervous system lymphoma (PCNSL) consists of 1%-5% of brain tumors, and the lesions can be identified using conventional techniques such as CT and MRI. However, differential diagnosis is still challenging when the lesions show atypical findings similar to other diseases such as glioma, infectious diseases (progressive multifocal leukoencephalopathy, toxoplasmosis), and demyelinating diseases (multiple sclerosis). In this review, we have presented imaging findings of conventional and advanced neuroimaging techniques to help differentiate PCNSL from other diseases and detect further characteristics such as prognostic factors, treatment effects, and gene mutations.


Assuntos
Sistema Nervoso Central , Linfoma , Humanos , Linfoma/diagnóstico por imagem
3.
Brain Nerve ; 73(10): 1107-1114, 2021 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-34615748

RESUMO

Management of primary central nervous system lymphoma (PCNSL) includes induction and consolidation therapies in newly diagnosed patients, as well as second-line therapy in relapsed or refractory patients. The current standard-of-care induction therapy involves methotrexate (MTX)-based multi-agent immunochemotherapy with rituximab, methotrexate, procarbazine, and vincristine. Deferral or dose reduction of radiation therapy is considered in consolidation therapy, especially in elderly patients who carry a high risk of radiation-induced delayed neurotoxicity. Since elderly patients comprise the main population of PCNSL, minimally toxic treatments that are effective and feasible for them are strongly needed. For second-line therapy, rechallenge using MTX-based chemotherapy (in patients with a prior durable response to MTX-based chemotherapy) or radiation therapy is considered. Bruton's tyrosine kinase inhibitor tirabrutinib (for relapsed and refractory PCNSL) and high-dose chemotherapy with autologous stem cell transplantation support using thiotepa and busulfan (BuTT) were approved by the Japanese Ministry of Health and Welfare in March 2020 and has recently become available for clinical practice. While these novel treatments seem promising, the optimal use of these treatments along with the standard-of-care therapy of PCNSL should be defined and investigated in clinical trials.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma , Idoso , Sistema Nervoso Central , Humanos , Japão , Linfoma/terapia , Transplante Autólogo
4.
J Headache Pain ; 22(1): 121, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34625019

RESUMO

BACKGROUND: Calcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response. CASES: We present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy. CONCLUSION: This case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Anticorpos Monoclonais/efeitos adversos , Calcitonina , Sistema Nervoso Central , Humanos , Transtornos de Enxaqueca/tratamento farmacológico
5.
Zhonghua Bing Li Xue Za Zhi ; 50(10): 1157-1162, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34619870

RESUMO

Objective: To investigate the clinicopathological features, immunophenotype, molecular genetics and prognosis of extraskeletal mesenchymal chondrosarcoma in central nerve system (CNS). Methods: The clinicopathological findings, immunohistochemistry and genetic analysis of four cases of extraskeletal mesenchymal chondrosarcoma in Xuanwu Hospital between 2014 and 2019 were reviewed and followed up. Results: The ages of patients ranged from 20-35 years. Three patients had intracranial lesions and one had intradural tumor. The characteristic histologic features were undifferentiated small cells together with scattered islands of hyaline cartilage. There was hemangiopericytoma-like pattern with calcification and ossification. The tumor cells were positive for VIM and SOX9; and the small cells were positive for CD99, NSE and NKX3.1. The cells in chondroid matrix were positive for S-100. All tumor cells were negative for markers including CKpan, EMA and desmin. At molecular analysis, HEY1-NCOA2 fusion transcripts were identified in three patients. The fusion points were between exon 4 of HEY1 and exon 13 of NCOA2. Follow-up information was obtained in two patients, and both were free from recurrence or metastasis at 8 and 20 months. Conclusions: Extraskeletal mesenchymaI chondrosarcoma is a rare CNS disease with poor prognosis. In addition to SOX9, NKX3.1 can be another useful antibody for the differential diagnosis. The combination of pathological characteristics, immunophenotype and genetic profile of tumor is essential for diagnosis.


Assuntos
Condrossarcoma Mesenquimal , Condrossarcoma , Hemangiopericitoma , Adulto , Sistema Nervoso Central , Condrossarcoma Mesenquimal/genética , Condrossarcoma Mesenquimal/cirurgia , Humanos , Imuno-Histoquímica , Adulto Jovem
6.
Expert Opin Pharmacother ; 22(15): 2019-2031, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34605345

RESUMO

Introduction: Treatments for brain cancer have radically evolved in the past decade due to a better understanding of the interplay between the immune system and tumors of the central nervous system (CNS). However, glioblastoma multiforme (GBM) remains the most common and lethal CNS malignancy affecting adults.Areas covered: The authors review the literature on glioblastoma pharmacologic therapies with a focus on trials of combination chemo-/immunotherapies and drug delivery platforms from 2015 to 2021.Expert opinion: Few therapeutic advances in GBM treatment have been made since the Food and Drug Administration (FDA) approval of the BCNU-eluting wafer, Gliadel, in 1996 and oral temozolomide (TMZ) in 2005. Recent advances in our understanding of GBM have promoted a wide assortment of new therapeutic approaches including combination therapy, immunotherapy, vaccines, and Car T-cell therapy along with developments in drug delivery. Given promising preclinical data, these novel pharmacotherapies for the treatment of GBM are currently being evaluated in various stages of clinical trials.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/tratamento farmacológico , Sistema Nervoso Central , Glioblastoma/tratamento farmacológico , Humanos , Prognóstico , Temozolomida/uso terapêutico , Estados Unidos
7.
Intern Med ; 60(20): 3299-3304, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34657908

RESUMO

Allogeneic hemopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for refractory hematological malignancies. However, there are many treatment-related complications, including organ disorders, graft-versus-host disease (GVHD), and infectious diseases. Furthermore, there are many unclear points regarding central nervous system (CNS) complications, and the prognosis in patients with CNS complications is extremely poor. We herein report a 49-year-old woman who developed CNS-GVHD after a second transplantation for therapy-related myelodysplastic syndrome. CNS-GVHD in this case was refractory to all treatments, including steroids, and progressed. We also present a review of the literature about the symptoms, diagnosis, and treatment of CNS-GVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Sistema Nervoso Central , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Transplante Homólogo/efeitos adversos
8.
BMC Genomics ; 22(1): 742, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649498

RESUMO

BACKGROUND: Damage to the adult central nervous system often leads to long-term disruptions in function due to the limited capacity for neurological recovery. The central nervous system of the Mediterranean field cricket, Gryllus bimaculatus, shows an unusual capacity for compensatory plasticity, most obviously in the auditory system and the cercal escape system. In both systems, unilateral sensory disruption leads the central circuitry to compensate by forming and/or strengthening connections with the contralateral sensory organ. While this compensatory plasticity in the auditory system relies on robust dendritic sprouting and novel synapse formation, the compensatory plasticity in the cercal escape circuitry shows little obvious dendritic sprouting and instead may rely on shifts in excitatory and inhibitory synaptic strength. RESULTS: In order to better understand what types of molecular pathways might underlie this compensatory shift in the cercal system, we used a multiple k-mer approach to assemble a terminal ganglion transcriptome that included ganglia collected one, three, and 7 days after unilateral cercal ablation in adult, male animals. We performed differential expression analysis using EdgeR and DESeq2 and examined Gene Ontologies to identify candidates potentially involved in this plasticity. Enriched GO terms included those related to the ubiquitin-proteosome protein degradation system, chromatin-mediated transcriptional pathways, and the GTPase-related signaling system. CONCLUSION: Further exploration of these GO terms will provide a clearer picture of the processes involved in compensatory recovery of the cercal escape system in the cricket and can be compared and contrasted with the distinct pathways that have been identified upon deafferentation of the auditory system in this same animal.


Assuntos
Gryllidae , Animais , Sistema Nervoso Central , Gryllidae/genética , Interneurônios , Masculino
9.
Epidemiol Mikrobiol Imunol ; 70(3): 189-198, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34641693

RESUMO

Tick-borne encephalitis (TBE) is a febrile illness caused by tick-borne encephalitis virus (TBEV), frequently manifesting as inflammation of the central nervous system. TBEV is a typical arbovirus, i.e., belongs to a group of viruses transmitted by blood-sucking arthropods. Taxonomically, TBEV is a member of the genus Flavivirus, family Flaviviridae. The disease is endemic in North Eurasia, from western Europe to East Asia. The virus occurs in natural foci of the disease all over Czechia, where it is transmitted predominantly by the castor bean tick (Ixodes ricinus). This infection has a potential to cause significant long-term disability affecting the quality of the patients life. Vaccine is available; however, vaccination coverage in Czechia is still low (around 30% of the total population). Lately, attention has been focused on new possibilities for early diagnosis and specific treatment, which so far has only been symptomatic or empirical.


Assuntos
Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos , Ixodes , Animais , Sistema Nervoso Central , Encefalite Transmitida por Carrapatos/diagnóstico , Encefalite Transmitida por Carrapatos/epidemiologia , Europa (Continente) , Humanos
10.
Neuron ; 109(19): 3069-3071, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34619086

RESUMO

Oligodendrocyte precursor cell differentiation into myelinating oligodendrocytes is critical for remyelination in the central nervous system after injury. In this issue of Neuron, Niu et al. (2021) detail a novel role for ring finger protein Rnf43, which is expressed in response to injury and is essential to promote remyelination in vivo.


Assuntos
Células Precursoras de Oligodendrócitos , Remielinização , Diferenciação Celular , Sistema Nervoso Central , Oligodendroglia
11.
Trop Biomed ; 38(3): 435-445, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34608117

RESUMO

Ever since the first reported case series on SARS-CoV-2-induced neurological manifestation in Wuhan, China in April 2020, various studies reporting similar as well as diverse symptoms of COVID-19 infection relating to the nervous system were published. Since then, scientists started to uncover the mechanism as well as pathophysiological impacts it has on the current understanding of the disease. SARS-CoV-2 binds to the ACE2 receptor which is present in certain parts of the body which are responsible for regulating blood pressure and inflammation in a healthy system. Presence of the receptor in the nasal and oral cavity, brain, and blood allows entry of the virus into the body and cause neurological complications. The peripheral and central nervous system could also be invaded directly in the neurogenic or hematogenous pathways, or indirectly through overstimulation of the immune system by cytokines which may lead to autoimmune diseases. Other neurological implications such as hypoxia, anosmia, dysgeusia, meningitis, encephalitis, and seizures are important symptoms presented clinically in COVID-19 patients with or without the common symptoms of the disease. Further, patients with higher severity of the SARS-CoV-2 infection are also at risk of retaining some neurological complications in the long-run. Treatment of such severe hyperinflammatory conditions will also be discussed, as well as the risks they may pose to the progression of the disease. For this review, articles pertaining information on the neurological manifestation of SARS-CoV-2 infection were gathered from PubMed and Google Scholar using the search keywords "SARS-CoV-2", "COVID-19", and "neurological dysfunction". The findings of the search were filtered, and relevant information were included.


Assuntos
COVID-19/patologia , Sistema Nervoso Central/patologia , Doenças do Sistema Nervoso/virologia , Sistema Nervoso Periférico/patologia , Enzima de Conversão de Angiotensina 2/metabolismo , Anosmia/virologia , Sistema Nervoso Central/virologia , Disgeusia/virologia , Encefalite Viral/virologia , Humanos , Meningite Viral/virologia , Doenças do Sistema Nervoso/patologia , Sistema Nervoso Periférico/virologia , SARS-CoV-2 , Convulsões/virologia
12.
BMC Genomics ; 22(1): 637, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479505

RESUMO

BACKGROUND: The pond snail, Lymnaea stagnalis (L. stagnalis), has served as a valuable model organism for neurobiology studies due to its simple and easily accessible central nervous system (CNS). L. stagnalis has been widely used to study neuronal networks and recently gained popularity for study of aging and neurodegenerative diseases. However, previous transcriptome studies of L. stagnalis CNS have been exclusively carried out on adult L. stagnalis only. As part of our ongoing effort studying L. stagnalis neuronal growth and connectivity at various developmental stages, we provide the first age-specific transcriptome analysis and gene annotation of young (3 months), adult (6 months), and old (18 months) L. stagnalis CNS. RESULTS: Using the above three age cohorts, our study generated 55-69 millions of 150 bp paired-end RNA sequencing reads using the Illumina NovaSeq 6000 platform. Of these reads, ~ 74% were successfully mapped to the reference genome of L. stagnalis. Our reference-based transcriptome assembly predicted 42,478 gene loci, of which 37,661 genes encode coding sequences (CDS) of at least 100 codons. In addition, we provide gene annotations using Blast2GO and functional annotations using Pfam for ~ 95% of these sequences, contributing to the largest number of annotated genes in L. stagnalis CNS so far. Moreover, among 242 previously cloned L. stagnalis genes, we were able to match ~ 87% of them in our transcriptome assembly, indicating a high percentage of gene coverage. The expressional differences for innexins, FMRFamide, and molluscan insulin peptide genes were validated by real-time qPCR. Lastly, our transcriptomic analyses revealed distinct, age-specific gene clusters, differentially expressed genes, and enriched pathways in young, adult, and old CNS. More specifically, our data show significant changes in expression of critical genes involved in transcription factors, metabolisms (e.g. cytochrome P450), extracellular matrix constituent, and signaling receptor and transduction (e.g. receptors for acetylcholine, N-Methyl-D-aspartic acid, and serotonin), as well as stress- and disease-related genes in young compared to either adult or old snails. CONCLUSIONS: Together, these datasets are the largest and most updated L. stagnalis CNS transcriptomes, which will serve as a resource for future molecular studies and functional annotation of transcripts and genes in L. stagnalis.


Assuntos
Perfilação da Expressão Gênica , Lymnaea , Animais , Sistema Nervoso Central , Lymnaea/genética , Anotação de Sequência Molecular , Transcriptoma
13.
Mater Sci Eng C Mater Biol Appl ; 128: 112253, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474815

RESUMO

Penetrating traumatic brain injury (pTBI) causes serious neurological deficits with no clinical regenerative therapies currently available. Tissue engineering strategies using biomaterial-based 'structural bridges' offer high potential to promote neural regeneration post-injury. This includes surgical grade materials which can be repurposed as biological scaffolds to overcome challenges associated with long approval processes and scaleup for human application. However, high throughput, pathomimetic models of pTBI are lacking for the developmental testing of such neuro-materials, representing a bottleneck in this rapidly emergent field. We have established a high throughput and facile culture model containing the major neural cell types which govern biomaterial handling in the central nervous system. We show that induction of traumatic injuries was feasible in the model, with post-injury implantation of a surgical grade biomaterial. Cellular imaging in lesions was achievable using standard epifluorescence microscopy methods. Key pathological features of pTBI were evident in vitro namely immune cell infiltration of lesions/biomaterial, with responses characteristic of cell scarring, namely hypertrophic astrocytes with GFAP upregulation. Based on our observations, we consider the high-throughput, inexpensive and facile pTBI model can be used to study biomaterial 'implantation' and evaluate neural cell-biomaterial responses. The model is highly versatile to test a range of laboratory and clinical grade materials for neural regeneration.


Assuntos
Materiais Biocompatíveis , Lesões Encefálicas Traumáticas , Materiais Biocompatíveis/farmacologia , Lesões Encefálicas Traumáticas/terapia , Sistema Nervoso Central , Humanos , Regeneração Nervosa , Engenharia Tecidual , Tecidos Suporte
14.
PLoS One ; 16(9): e0255950, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34506501

RESUMO

SARS-CoV-2 affects mainly the lungs, however, other manifestations, including neurological manifestations, have also been described during the disease. Some of the neurological findings have involved intracerebral or subarachnoid hemorrhage, strokes, and other thrombotic/hemorrhagic conditions. Nevertheless, the gross pathology of hemorrhagic lesions in the central nervous system has not been previously described in Brazilian autopsy cases. This study aimed to describe gross and microscopic central nervous system (CNS) pathology findings from the autopsies and correlate them with the clinical and laboratory characteristics of forty-five patients with COVID-19 from Manaus, Amazonas, Brazil. Forty-four patients were autopsied of which thirty-eight of these (86.36%) were positive by RT-PCR for COVID-19, and six (13.3%) were positive by the serological rapid test. Clinical and radiological findings were compatible with the infection. The patients were classified in two groups: presence (those who had hemorrhagic and/or thrombotic manifestations in the CNS) and absence (those who did not present hemorrhagic and/or thrombotic manifestations in the CNS). For risk assessment, relative risk and respective confidence intervals were estimated. Macroscopic or microscopic hemorrhages were found in twenty-three cases (52,27%). The postmortem gross examination of the brain revealed a broad spectrum of hemorrhages, from spots to large and confluent areas and, under microscopy, we observed mainly perivascular discharge. The association analyses showed that the use of corticosteroid, anticoagulant and antibiotic had no statistical significance with a risk of nervous system hemorrhagic manifestations. However, it is possible to infer a statistical tendency that indicates that individuals with diabetes had a higher risk for the same outcome (RR = 1.320, 95% CI = 0.7375 to 2.416, p = 0.3743), which was not observed in relation to other comorbidities. It is unknown whether the new variants of the virus can cause different clinical manifestations, such as those observed or indeed others. As a result, more studies are necessary to define clinical and radiologic monitoring protocols and strategic interventions for patients at risk of adverse and fatal events, such as the extensive hemorrhaging described here. It is imperative that clinicians must be aware of comorbidities and the drugs used to treat patients with COVID-19 to prevent CNS hemorrhagic and thrombotic events.


Assuntos
COVID-19/epidemiologia , Sistema Nervoso Central/patologia , Hemorragia/epidemiologia , Trombose/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Adv Exp Med Biol ; 1345: 241-252, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34582027

RESUMO

The nervous system is an ensemble of organs that transmit and process external information and are responsible for the adaption to the external environment and homeostasis control of the internal environment. The nervous system of vertebrates is divided into the central nervous system (CNS) and peripheral nervous system (PNS) due to its structural features. The CNS, which includes the brain and the spinal cord, processes information from external stimuli and assembles orders suitable for these stimuli. The CNS then sends signals to control other organs/tissues. On the other hand, the PNS connects the CNS to other organs/tissues and functions as a signal pathway. Therefore, the decline and loss of various functions due to injuries of the nervous system cause an impaired quality of life (QOL) and eventually the termination of life activities. Here, we report mainly on decellularized neural tissue and its application as a substrate for the regeneration of the nervous system.


Assuntos
Tecido Nervoso , Qualidade de Vida , Animais , Sistema Nervoso Central , Regeneração Nervosa , Sistema Nervoso Periférico , Medula Espinal
16.
Nat Immunol ; 22(10): 1280-1293, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34556874

RESUMO

Traumatic brain injury (TBI) and cerebrovascular injury are leading causes of disability and mortality worldwide. Systemic infections often accompany these disorders and can worsen outcomes. Recovery after brain injury depends on innate immunity, but the effect of infections on this process is not well understood. Here, we demonstrate that systemically introduced microorganisms and microbial products interfered with meningeal vascular repair after TBI in a type I interferon (IFN-I)-dependent manner, with sequential infections promoting chronic disrepair. Mechanistically, we discovered that MDA5-dependent detection of an arenavirus encountered after TBI disrupted pro-angiogenic myeloid cell programming via induction of IFN-I signaling. Systemic viral infection similarly blocked restorative angiogenesis in the brain parenchyma after intracranial hemorrhage, leading to chronic IFN-I signaling, blood-brain barrier leakage and a failure to restore cognitive-motor function. Our findings reveal a common immunological mechanism by which systemic infections deviate reparative programming after central nervous system injury and offer a new therapeutic target to improve recovery.


Assuntos
Anti-Infecciosos/imunologia , Lesões Encefálicas Traumáticas/imunologia , Sistema Nervoso Central/imunologia , Imunidade Inata/imunologia , Animais , Barreira Hematoencefálica/imunologia , Encéfalo/imunologia , Modelos Animais de Doenças , Feminino , Interferon Tipo I/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/imunologia
17.
Nat Commun ; 12(1): 5219, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471138

RESUMO

Microglia, the resident immune cells of the central nervous system, are key players in healthy brain homeostasis and plasticity. In neurological diseases, such as Multiple Sclerosis, activated microglia either promote tissue damage or favor neuroprotection and myelin regeneration. The mechanisms for microglia-neuron communication remain largely unkown. Here, we identify nodes of Ranvier as a direct site of interaction between microglia and axons, in both mouse and human tissues. Using dynamic imaging, we highlight the preferential interaction of microglial processes with nodes of Ranvier along myelinated fibers. We show that microglia-node interaction is modulated by neuronal activity and associated potassium release, with THIK-1 ensuring their microglial read-out. Altered axonal K+ flux following demyelination impairs the switch towards a pro-regenerative microglia phenotype and decreases remyelination rate. Taken together, these findings identify the node of Ranvier as a major site for microglia-neuron interaction, that may participate in microglia-neuron communication mediating pro-remyelinating effect of microglia after myelin injury.


Assuntos
Microglia/fisiologia , Neurônios/fisiologia , Potássio/metabolismo , Nós Neurofibrosos/fisiologia , Remielinização/fisiologia , Animais , Axônios , Encéfalo , Receptor 1 de Quimiocina CX3C , Sistema Nervoso Central , Doenças Desmielinizantes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla , Bainha de Mielina/fisiologia , Neuroproteção
18.
J Biomed Nanotechnol ; 17(8): 1459-1485, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544527

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare but highly aggressive subtype of extra nodal non-Hodgkin lymphoma (NHL), which is confined in the central nervous system (CNS). Despite recent advancements in treatment options, the overall prognosis of PCNSL remains poor. Among many unfavorable factors affecting efficacy, inadequate drug delivery into the CNS is still the thorniest challenge. Blood-brain barrier (BBB) constitutes a significant impediment, restricting entry of most therapeutics to the brain. Nanotechnology has offered great promise for brain diseases, as various nano-based drug delivery systems (NDDSs) have been developed for delivery of theranostic agents in to the CNS. These drug delivery systems possess significant advantages, including good feasibility, reliable safety profile, excellent BBB penetration and potent antitumor effects. As for treatment of PCNSL, numerous well-developed BBB-crossing nano-based strategies can be applied with proper modifications and improvements. Some exquisitely designed NDDSs specific for PCNSL have shown great potential. In this review, we provide a summary on current status of diagnosis and treatment of PCNSL, followed by an overview of BBB-crossing strategies applied in management of PCNSL, both novel and wellestablished. Finally, challenges and future perspectives in this field are also discussed.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma não Hodgkin , Barreira Hematoencefálica , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Humanos , Nanomedicina
19.
Eur J Radiol ; 143: 109945, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34492625

RESUMO

OBJECTIVE: To investigate the role of quantitative muscle biomarkers assessed with skeletal muscle index at the third lumbar vertebra (L3-SMI) and temporal muscle thickness (TMT) in predicting progression-free and overall survival in patients with primary central nervous system lymphoma (PCNSL) undergoing first-line high-dose methotrexate-based chemotherapy. METHODS: L3-SMI and TMT were calculated on abdominal CT and brain high-resolution 3D-T1-weighted MR images, respectively, using predefined validated methods. Standardized sex-specific cut-off values were used to divide patients in different risk categories. Kaplan-Meier plots were calculated, and survival analysis was performed using log-rank tests, univariate, and multivariable Cox-regression models, calculating hazard ratios (HR) and 95% confidence intervals (CI), also adjusting for potential confounders (age, sex, and performance status). RESULTS: Forty-three patients were included in this study. Median follow-up was 23 months (interquartile range 12-40); at median follow-up, rates of progression-free and overall survival for the cohort were 46% and 57%, respectively. Thirteen (30%) and 11 (26%) patients showed L3-SMI or TMT values below the predefined cut-offs. In Cox-regression multivariable analysis patients with low L3-SMI or TMT showed significantly worse progression-free (HR 4.40, 95% CI 1.66-11.61, p = 0.003; HR 4.40, 95% CI 1.68-11.49, p = 0.003, respectively) and overall survival (HR 3.16, 95% CI 1.09-9.11, p = 0.034; HR 4.93, 95% CI 1.78-13.65, p = 0.002, respectively) compared to patients with high L3-SMI or TMT. CONCLUSIONS: Quantitative muscle mass evaluation assessed by both L3-SMI and TMT is a promising tool to identify PCNSL patients at high risk of negative outcome. Confirmatory studies on larger independent series are warranted.


Assuntos
Linfoma não Hodgkin , Sarcopenia , Biomarcadores , Sistema Nervoso Central , Feminino , Humanos , Linfoma não Hodgkin/patologia , Masculino , Músculo Esquelético/patologia , Prognóstico , Estudos Retrospectivos , Sarcopenia/patologia , Músculo Temporal , Tomografia Computadorizada por Raios X
20.
Nat Commun ; 12(1): 5489, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531391

RESUMO

Intraspecific competition is a major force in mediating population dynamics, fuelling adaptation, and potentially leading to evolutionary diversification. Among the evolutionary arms races between parasites, one of the most fundamental and intriguing behavioural adaptations and counter-adaptations are superparasitism and superparasitism avoidance. However, the underlying mechanisms and ecological contexts of these phenomena remain underexplored. Here, we apply the Drosophila parasite Leptopilina boulardi as a study system and find that this solitary endoparasitic wasp provokes a host escape response for superparasitism avoidance. We combine multi-omics and in vivo functional studies to characterize a small set of RhoGAP domain-containing genes that mediate the parasite's manipulation of host escape behaviour by inducing reactive oxygen species in the host central nervous system. We further uncover an evolutionary scenario in which neofunctionalization and specialization gave rise to the novel role of RhoGAP domain in avoiding superparasitism, with an ancestral origin prior to the divergence between Leptopilina specialist and generalist species. Our study suggests that superparasitism avoidance is adaptive for a parasite and adds to our understanding of how the molecular manipulation of host behaviour has evolved in this system.


Assuntos
Drosophila melanogaster/parasitologia , Proteínas Ativadoras de GTPase/genética , Interações Hospedeiro-Parasita/genética , Proteínas de Insetos/genética , Vespas/genética , Vespas/patogenicidade , Animais , Aprendizagem da Esquiva , Comportamento Animal , Coevolução Biológica , Sistema Nervoso Central/parasitologia , Ingestão de Alimentos , Feminino , Proteínas Ativadoras de GTPase/classificação , Proteínas Ativadoras de GTPase/metabolismo , Expressão Gênica , Proteínas de Insetos/classificação , Proteínas de Insetos/metabolismo , Larva/parasitologia , Masculino , Família Multigênica , Espécies Reativas de Oxigênio/metabolismo , Vespas/metabolismo
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