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1.
Ann Clin Transl Neurol ; 10(8): 1353-1364, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37329177

RESUMO

OBJECTIVE: The prognosis for patients presenting with a large ischemic core (LIC) following endovascular thrombectomy is relatively poor. This study aimed to construct and validate a nomogram for predicting 3-month unfavorable outcome in patients with anterior circulation occlusion-related LIC who underwent endovascular thrombectomy. METHODS: A retrospective training cohort and a prospective validation cohort of patients with a large ischemic core were studied. The diffusion weighted imaging related radiomic features and pre-thrombectomy clinical features were collected. After the selection of relevant features, a nomogram predicting modified Rankin Scale score of 3-6 as an unfavorable outcome was established. The discriminatory value of the nomogram was evaluated with a receiver operating characteristic curve. RESULTS: A total of 140 patients (mean age 66.3 ± 13.4 years, 35% female) were included in this study, consisting of a training cohort (n = 95) and a validation cohort (n = 45). The percentage of patients with an mRS scores of 0-2 was 30%, 0-3 was 40.7%, and 32.9% were dead. Age, National Institute of Health Stroke Scale (NIHSS) score, and two radiomic features, Maximum2DDiameterColumn and Maximum2DDiameterSlice, were identified as factors associated with unfavorable outcome in the nomogram. The nomogram demonstrated an area under the curve of 0.892 (95% confidence interval [CI], 0.812-0.947) in the training dataset and 0.872 (95% CI, 0.739-0.953) in the validation dataset. INTERPRETATION: This nomogram, which includes age, NIHSS score, Maximum2DDiameterColumn, and Maximum2DDiameterSlice, may predict the risk of unfavorable outcome in patients with LIC caused by anterior circulation occlusion.


Assuntos
Imagem de Difusão por Ressonância Magnética , Nomogramas , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Estudos Retrospectivos , Curva ROC , Trombectomia/efeitos adversos
2.
Microbiol Spectr ; 9(3): e0076921, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34908504

RESUMO

Cerebrospinal fluid (CSF) circulating in the human central nervous system has long been considered aseptic in healthy individuals, because normally, the blood-brain barrier can protect against microbial invasions. However, this dogma has been called into question by several reports that microbes were identified in human brains, raising the question of whether there is a microbial community in the CSF of healthy individuals without neurological diseases. Here, we collected CSF samples and other samples, including one-to-one matched oral and skin swab samples (positive controls), from 23 pregnant women aged between 23 and 40 years. Normal saline samples (negative controls), sterile swabs, and extraction buffer samples (contamination controls) were also collected. Twelve of the CSF specimens were also used to evaluate the physiological activities of detected microbes. Metagenomic and metatranscriptomic sequencing was performed in these 116 specimens. A total of 620 nonredundant microbes were detected, which were dominated by bacteria (74.6%) and viruses (24.2%), while in CSF samples, metagenomic sequencing found only 26 nonredundant microbes, including one eukaryote, four bacteria, and 21 viruses (mostly bacteriophages). The beta diversity of microbes compared between CSF metagenomic samples and other types of samples (except negative controls) was significantly different from that of the CSF self-comparison. In addition, there was no active or viable microbe in the matched metagenomic and metatranscriptomic sequencing of CSF specimens after subtracting those also found in normal saline, DNA extraction buffer, and skin swab specimens. In conclusion, our results showed no strong evidence of a colonized microbial community present in the CSF of healthy individuals. IMPORTANCE The microbiome is prevalent throughout human bodies, with profound health implications. However, it remains unclear whether it is present and active in human CSF, which has been long considered aseptic due to the blood-brain barrier. Here, we applied unbiased metagenomic and metatranscriptomic sequencing to detect the presence of a microbiome in CSF collected from 23 pregnant women with matched controls. Analysis of 116 specimens found no strong evidence to support the presence of a colonized microbiome in CSF. Our findings will strengthen our understanding of the internal environment of the CSF in healthy people, which has strong implications for human health, especially for neurological infections and disorders, and will help further disease diagnostics, prevention, and therapeutics in clinical settings.


Assuntos
Bactérias/isolamento & purificação , Bacteriófagos/isolamento & purificação , Líquido Cefalorraquidiano/microbiologia , Adulto , Bactérias/classificação , Bactérias/genética , Barreira Hematoencefálica/microbiologia , DNA Bacteriano/líquido cefalorraquidiano , DNA Viral/líquido cefalorraquidiano , Feminino , Voluntários Saudáveis , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metagenoma/genética , Metagenômica , Microbiota , Gravidez
3.
Front Neurol ; 11: 586905, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33281724

RESUMO

Intracerebral hemorrhage (ICH) is a fatal subtype of stroke, and effective interventions to improve the functional outcomes are still lacking. Suppressor of cytokine signaling 3 (SOCS3) plays critical roles in the inflammatory response by negatively regulating cytokine-Jak-Stat signaling. However, the role of SOCS3 in the regulation of macrophage polarization is highly controversial and the fine regulation exerted by SOCS3 needs further understanding. In this study, rat ICH models were established by infusion of collagenase into the caudate nucleus. To decrease SOCS3 expression into microglia/macrophages in the hemorrhagic lesion area, we injected lentiviral short hairpin RNA (shSOCS3) (Lenti-shSOCS3) into the hematoma cavity at 24 h following ICH. We found that the number of iNOS-positive cells (M1 phenotype) was significantly reduced, whereas arginase-1-positive cells (M2 phenotype) were markedly elevated in animals that received Lenti-shSOCS3 injections compared with those in the Lenti-EGFP and saline groups. The increase in arginase-1-positive cells was associated with a significantly lower pro-inflammatory microenvironment, which included the downregulation of pro-inflammatory cytokines [interleukin (IL)-1ß, IL-6, and TNF-α] and concurrent upregulation of anti-inflammatory (IL-10) mediators. In addition, this marked shift toward the M2 phenotype was associated with suppressed NF-κB activation. Furthermore, these changes notably enhanced the neuroprotective effects and functional recovery in Lenti-shSOCS3-injected animals. Our findings indicated that reduction in SOCS3 expression caused a marked bias toward the M2 phenotype and ameliorated the inflammatory microenvironment, which enhanced neuroprotective effects and resulted in notable improvement in functional recovery after ICH.

4.
Data Brief ; 31: 105700, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32478153

RESUMO

This data can serve as a reference for other next-generation sequencing (NGS) of the cerebrospinal fluid (CSF). In the related research article, entitled "Next-Generation Sequencing of Cerebrospinal Fluid for the Diagnosis of Neurocysticercosis", we reported NGS of the CSF might be an auxiliary method for neurocysticercosis (NCC) patients who have complicated manifestations and courses to receive early diagnosis and treatment. In this article, we retrieved the available data about the sequencing statistics of the CSF samples and the number of unique reads and genomic coverage aligning to microorganic sequences. The data were generated by the Illumina MiniSeq system for sequencing and computational subtraction of the human host sequences was performed. Finally, the remaining sequencing data were aligned to the Microbial Genome Databases. This data can serve as a reference for other NGS of the CSF.

5.
Clin Neurol Neurosurg ; 193: 105752, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32220712

RESUMO

OBJECTIVE: Neurocysticercosis (NCC) is the most common parasitic disease of the human central nervous system (CNS). However, a diagnosis of NCC may be hard to make if the specific clinical and routine neuroimaging manifestations are lacking, which hinders physicians from considering further immunodiagnostic tests. PATIENTS AND METHODS: Seven patients presented with fever, headache, nausea, cognitive decline, confusion, or progressive leg weakness. There were no pathogens found in the cerebrospinal fluid (CSF); patients were clinically suspected of meningoencephalitis or cerebrovascular disease. To clearly determine the etiology, next generation sequencing (NGS) of the CSF was used to detect pathogens in these seven patients. RESULTS: Taenia solium DNA sequences were detected in the seven patients, but not in the non-template controls (NTCs) or the other patients with clinically suspected CNS infections. Based on the patients' medical data and the diagnostic criteria for NCC, seven patients were diagnosed with probable NCC. The unique reads aligning to Taenia solium ranged from 6 to 261064, with genomic coverage ranging from 0.0003% to 14.8079%. The number of unique reads and genomic coverage dropped in three of the seven patients after antiparasitic treatment, consistent with the relief of symptoms. CONCLUSION: This study showed that NGS of the CSF might be an auxiliary diagnostic method for NCC patients. Larger studies are required.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neurocisticercose/líquido cefalorraquidiano , Neurocisticercose/diagnóstico , Adulto , Idoso , Animais , Antiparasitários/uso terapêutico , Líquido Cefalorraquidiano/química , Líquido Cefalorraquidiano/parasitologia , DNA de Protozoário/química , DNA de Protozoário/genética , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurocisticercose/parasitologia , Neuroimagem , Taenia solium/genética
6.
J Mol Neurosci ; 70(5): 659-666, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32002752

RESUMO

Metagenomics next-generation sequencing (mNGS) is increasingly available for the detection of obscure infectious diseases of the central nervous system. However, human DNA contamination from elevated white cells, one of the characteristic cerebrospinal fluid (CSF) features in meningitis patients, greatly reduces the sensitivity of mNGS in the pathogen detection. Currently, effective approaches to selectively reduce host DNA contamination from clinical CSF samples are still lacking. In this study, a total of 20 meningitis patients were enrolled, including 10 definitively diagnosed tuberculous meningitis (TBM) and 10 definite cryptococcal meningitis (CM) cases. To evaluate the effect of reduced human DNA in the sensitivity of mNGS detection, three specimen-processing protocols were performed: (i) To remove human DNA, saponin, a nonionic surfactant, was used to selectively lyse white cells in CSF followed by DNase treatment prior to the extraction of DNA; (ii) to reduce host DNA, CSF was centrifuged to remove human cells, and the supernatant was collected for DNA extraction; and (iii) DNA extraction from the unprocessed specimens was set as the control. We found that saponin processing significantly elevated the NGS unique reads for Cryptococcus (P < 0.01) compared with the control but had no effects for Mycobacterium tuberculosis (P > 0.05). However, detection of centrifuged supernatants improved the NGS unique reads for both TBM and CM compared with controls (P < 0.01). Our results demonstrate that the use of mNGS of centrifuged supernatants from clinical CSF samples in patients with TBM and CM is a simple and effective method to improve the sensitivity of pathogen detection.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Meningite Criptocócica/microbiologia , Metagenômica/métodos , Técnicas de Diagnóstico Molecular/métodos , Análise de Sequência de DNA/métodos , Tuberculose Meníngea/microbiologia , Adulto , Idoso , Líquido Cefalorraquidiano/microbiologia , Cryptococcus/genética , Cryptococcus/patogenicidade , Feminino , Genoma Bacteriano , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala/normas , Humanos , Masculino , Meningite Criptocócica/líquido cefalorraquidiano , Meningite Criptocócica/diagnóstico , Metagenômica/normas , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/normas , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade , Sensibilidade e Especificidade , Análise de Sequência de DNA/normas , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/diagnóstico
7.
Front Neurosci ; 12: 582, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30210273

RESUMO

Infrasound, a kind of ambient noise, can cause severe disorders to various human organs, specially to central nervous system (CNS). Our previous studies have shown that infrasound-induced CNS injury was closely related with astrocytes activation and astrocytes-mediated neuroinflammation, but the underlying molecular mechanisms are still largely unclear. FGF2/FGFR1 (Fibroblast growth factor 2/Fibroblast growth factor receptor 1) pathway was reported to play an important role in anti-inflammation in CNS disorders. To further study the possible roles of FGF2/FGFR1 pathway in infrasound-induced CNS injury, here we exposed Sprague-Dawley rats or cultured astrocytes to 16 Hz, 150 dB infrasound, and explored the effects of FGF2 on infrasound-induced astrocytes activation and neuroinflammation. Western blotting, immunofluorescence and liquid chip method were used in this experiment. Our results showed that after 3- or 7-day exposure (2 h/day) of rats as well as 2 h exposure of cultured astrocytes to 16 Hz, 150 dB infrasound, astrocyte-expressed FGFR1 was downregulated in vivo and in vitro. FGF2 pretreatment not only inhibited infrasound-induced astrocyte activation in rat hippocampal CA1 region, but also reduced the levels of pro-inflammatory cytokines, such as TNF-α, IL-1ß, IL-18, IL-6, and IFN-γ in vitro and in vivo. However, FGF2 significantly upregulated the expression of FGFR1. Furthermore, we showed that FGF2 could attenuate IκBα phosphorylation, NF-κB p65 translocation, pro-inflammatory cytokines levels, and neuronal loss in the CA1 region induced by infrasound. On the contrary, PD173074, a special antagonist of FGFR1, could reverse the effects above in vitro and in vivo. Taken together, our findings showed that FGF2/FGFR1 pathway may exert inhibitive effects on astrocyte-mediated neuroinflammation in vitro and in vivo after infrasound exposure.

8.
Sci Rep ; 7: 45989, 2017 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-28383046

RESUMO

Complement activation plays important roles in the pathogenesis of central nervous system (CNS) diseases. Patients face neurological disorders due to the development of complement activation, which contributes to cell apoptosis, brain edema, blood-brain barrier dysfunction and inflammatory infiltration. We previously reported that induced neural stem cells (iNSCs) can promote neurological functional recovery in closed head injury (CHI) animals. Remarkably, we discovered that local iNSC grafts have the potential to modulate CNS inflammation post-CHI. In this study, we aimed to explore the role of systemically delivered iNSCs in complement activation following CNS injury. Our data showed that iNSC grafts decreased the levels of sera C3a and C5a and down-regulated the expression of C3d, C9, active Caspase-3 and Bax in the brain, kidney and lung tissues of CHI mice. Furthermore, iNSC grafts decreased the levels of C3d+/NeuN+, C5b-9+/NeuN+, C3d+/Map2+ and C5b-9+/Map2+ neurons in the injured cortices of CHI mice. Subsequently, we explored the mechanisms underlying these effects. With flow cytometry analysis, we observed a dramatic increase in complement receptor type 1-related protein y (Crry) expression in iNSCs after CHI mouse serum treatment. Moreover, both in vitro and in vivo loss-of-function studies revealed that iNSCs could modulate complement activation via Crry expression.


Assuntos
Ativação do Complemento/imunologia , Traumatismos Cranianos Fechados/imunologia , Traumatismos Cranianos Fechados/terapia , Células-Tronco Neurais/citologia , Células-Tronco Neurais/transplante , Transplante de Células-Tronco , Animais , Barreira Hematoencefálica/patologia , Caspase 3/metabolismo , Proteínas do Sistema Complemento/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Edema/patologia , Traumatismos Cranianos Fechados/sangue , Traumatismos Cranianos Fechados/patologia , Inflamação/patologia , Camundongos , Neurônios/metabolismo , Infiltração de Neutrófilos , Especificidade de Órgãos , Permeabilidade , Receptores de Complemento/metabolismo , Receptores de Complemento 3b , Proteína X Associada a bcl-2/metabolismo
9.
CNS Neurosci Ther ; 22(10): 824-35, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27390192

RESUMO

BACKGROUND: Edaravone is widely used for treating ischemic stroke, but it is not still confirmed in intracerebral hemorrhage (ICH) as an ideal medication targeting the brain parenchyma. We aimed to investigate the neuroprotective effects of stereotactic administration of edaravone (SI) into the brain parenchyma. METHODS: Intracerebral hemorrhage rat models were established by infusion of collagenase into the caudate nucleus. Neural functional recovery was assessed using modified neurological severity scores (mNSS). A comparative study of therapeutic effects between SI and intraperitoneal injection of edaravone (IP) involved in cerebral edema, blood-brain barrier (BBB) permeability, hematoma absorption, inflammatory response and neuronal apoptosis. RESULTS: Compared with IP, the mNSS was significantly (P < 0.05) improved by SI; cerebral edema and BBB permeability were dramatically ameliorated (P < 0.05); IL-4 and IL-10 levels increased, but IL-1ß and TNF-α levels significantly decreased; neuron apoptosis decreased markedly (P < 0.05); and caspase-3 and Bax expression significantly dropped, but Bcl-2 increased in SI group (P < 0.05). CONCLUSION: SI markedly improved neurological deficits in ICH rat models via antiinflammatory and antiapoptosis mechanisms and promoted M2-type microglia differentiation. SI was effective in rats with collagenase-induced ICH.


Assuntos
Antipirina/análogos & derivados , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/tratamento farmacológico , Colagenases/toxicidade , Sequestradores de Radicais Livres/administração & dosagem , Animais , Antipirina/administração & dosagem , Apoptose/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/fisiopatologia , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Citocinas/metabolismo , Modelos Animais de Doenças , Edaravone , Imageamento por Ressonância Magnética , Masculino , Microglia/metabolismo , Microglia/patologia , Proteínas do Tecido Nervoso/metabolismo , Ratos , Ratos Sprague-Dawley , Técnicas Estereotáxicas , Fatores de Tempo , Resultado do Tratamento
10.
Cell Mol Neurobiol ; 35(6): 881-90, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25840805

RESUMO

There is much evidence to suggest that brain-derived neurotrophic factor (BDNF) is a prominent candidate in promoting neuroprotection, axonal regeneration, and synaptic plasticity following spinal cord injury (SCI). Although some evidence indicates that BDNF has potent anti-oxidative effects and may be involved in the regulation of the immune response, the effects of BDNF in the inflammatory response during the course of secondary damage after SCI is still unclear. The present study was designed to investigate the effects of BDNF with a special focus on their effect on macrophage polarization after SCI. Adult C57 mice underwent T10 spinal cord clip compression injury and received lenti-BDNF vector injections at the epicenter of the lesion site. Four days later, total BDNF levels were greatly increased in animals that received lenti-BDNF injections. Confocal imaging showed that more than 80 % of the lenti-virus infected cells were CD11b-positive macrophages. In addition, the expression of arginase-1 and CD206 (associated with M2 macrophage phenotype) significantly increased in the animals that received lenti-BDNF injections compared with those that received lenti-EGFP injections. On the contrary, the expression of CD16/32 and inducible nitric oxide synthase (M1 phenotype marker) was down-regulated as demonstrated using flow cytometry and immunohistochemistry. Furthermore, the production of interleukin 1ß and tumor necrosis factor alpha was significantly reduced whereas the levels of interleukin 10 and interleukin 13 were elevated in subjects that received lenti-BDNF vector injections. The time course of functional recovery revealed that gradual recovery was observed in the subacute phase in lenti-BDNF group, little improvement was observed in lenti-EGFP group. At the axonal level, significant retraction of the CST axons were observed in lenti-EGFP injected animals relative to lenti-BDNF group by biotinylated dextran amine tracing. In addition, compared to lenti-BDNF group markedly demyelination was observed in the lenti-EGFP group using luxol fast blue staining. In conclusion, we found that BDNF could promote the shift of M1 to M2 phenotype and ameliorate the inflammatory microenvironment. Furthermore, the roles of BDNF in immunity modulation may enhance neuroprotective effects and partially contribute to the locomotor functional recovery after SCI.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/administração & dosagem , Fator Neurotrófico Derivado do Encéfalo/genética , Terapia Genética/métodos , Macrófagos/fisiologia , Mielite/prevenção & controle , Traumatismos da Medula Espinal/terapia , Animais , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Polaridade Celular/efeitos dos fármacos , Feminino , Técnicas de Transferência de Genes , Vetores Genéticos , Injeções Intralesionais , Injeções Espinhais , Lentivirus/genética , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/genética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mielite/genética , Mielite/patologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/patologia
11.
Drug Dev Ind Pharm ; 41(8): 1328-37, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25133664

RESUMO

The purpose of this study was to find a suitable method to increase the dissolution of disulfiram (DSF) which is easily decomposed. The dissolution of DSF within 1 h was significantly increased from 37% to >90% by co-milling with Aerosil® 200 pharm (Aerosil) and the increased dissolution remained stable during long-term storage while there was no significant degradation of DSF. By monitoring the changes in particle size of the grinding mixture, a mosaic DSF-in-Aerosil structure was demonstrated. The core size of the mosaic DSF/Aerosil system was 3.625 µm. The particle size of DSF was reduced from 20.75 µm to ∼200 nm and the size of the mosaic DSF/Aerosil system (3.625∼7.956 µm) increased on increasing the drug-loading content. Differential scanning calorimetry and X-ray powder diffraction analysis confirmed the largely amorphous state of DSF in the mosaic drug/carrier system. Fourier transform infrared spectroscopy confirmed the presence of hydrogen bonding between DSF and Aerosil. Scanning electron microscopy and transmission electron microscopy verified the DSF-in-Aerosil relationship in the particle size determination at different size levels. The possible mechanisms of dry milling included the hypothesis that during impact and collision, DSF particles melted into the surface of Aerosil turning them into an amorphous state or they became inlayed into the interspaces of the Aerosil structure with a much smaller size.


Assuntos
Dissulfiram/química , Nanopartículas/química , Dióxido de Silício/química , Cristalografia por Raios X , Tamanho da Partícula , Solubilidade , Difração de Raios X
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