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1.
Medicine (Baltimore) ; 98(26): e16118, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261528

RESUMO

To explore the growth trend of fetal lateral ventricular volume, for understanding the relationship between atrial diameter (AD) and volume in normal fetus and fetus with ventriculomegaly.Overall, 97 sequential fetal head magnetic resonance imaging scans were performed; these pertained to 50 fetuses with normal lateral ventricles [normal group; gestational age (GA): 24-38 weeks] and 47 fetuses with ventriculomegaly (VM) (VM group; GA: 24-37 weeks). The left, right, and total lateral ventricular volume were measured using 3-dimensional magnetic resonance hydrography (MRH). Correlation coefficient (r) was calculated to assess the relationships of measurements. Lineal regression analysis was used to assess correlation of AD and GA with volume. Between-group differences in terms of AD and volume were assessed using t test.Significant linear growth was observed in the total lateral ventricular volume compared with GA in the normal group with a relative growth rate of 2.87% per week (P <.001). Significant linear relationship between AD and volume was observed, and a significant equation was acquired in the normal group and VM groups, respectively, using the simple linear regression model: left volume = 0.438 * normal left diameter (NLD) + 1.359; right volume = 0.493 * normal right diameter (NRD) + 1.012; left volume = 0.959 * left diameter in VM (VLD) - 2.074; right volume = 0.799 * right diameter in VM (VRD) - 0.443. A significant equation was obtained in the normal group and the VM group, using the multiple linear regression model: Total volume (mL) = 0.396 * NLD + 0.410 * NRD + 3.101; and total volume = 0.989 * VLD + 0.834 * VRD - 3.141, respectively. In terms of AD and volume, the left lateral ventricle was significantly larger than the right side in both groups. The volume of lateral ventricle in AD ≥10 mm group was larger than that in the AD <10 mm group. The total volume in the VM group was significantly larger than that in the normal group.The total lateral ventricular volume increased with GA. AD can be used to evaluate the fetal ventricular volume.


Assuntos
Hidrocefalia/diagnóstico por imagem , Hidrocefalia/embriologia , Ventrículos Laterais/diagnóstico por imagem , Ventrículos Laterais/embriologia , Feminino , Humanos , Hidrocefalia/patologia , Ventrículos Laterais/patologia , Imagem por Ressonância Magnética , Tamanho do Órgão , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Diagnóstico Pré-Natal , Estudos Prospectivos
2.
BMC Neurol ; 19(1): 134, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31215432

RESUMO

BACKGROUND: CIC-mutant oligodendroglial tumours linked to better prognosis. We aim to investigate associations between CIC gene mutation status, MR characteristics and clinical features. METHODS: Imaging and genomic data from the Cancer Genome Atlas and the Cancer Imaging Archive (TCGA/TCIA) for 59 patients with oligodendroglial tumours were used. Differences between CIC mutation and CIC wild-type were tested using Chi-square test and binary logistic regression analysis. RESULTS: In univariate analysis, the clinical variables and MR features, which consisted 3 selected features (subventricular zone[SVZ] involvement, volume and seizure history) were associated with CIC mutation status (all p < 0.05). A multivariate logistic regression analysis identified that seizure history (no vs. yes odd ratio [OR]: 28.960, 95 confidence interval [CI]:2.625-319.49, p = 0.006) and SVZ involvement (SVZ- vs. SVZ+ OR: 77.092, p = 0.003; 95% CI: 4.578-1298.334) were associated with a higher incidence of CIC mutation status. The nomogram showed good discrimination, with a C-index of 0.906 (95% CI: 0.812-1.000) and was well calibrated. SVZ- group has increased (SVZ- vs. SVZ+, hazard ratio [HR]: 4.500, p = 0.04; 95% CI: 1.069-18.945) overall survival. CONCLUSIONS: Absence of seizure history and SVZ involvement (-) was associated with a higher incidence of CIC mutation.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/genética , Glioma/patologia , Proteínas Repressoras/genética , Adulto , Idoso , Neoplasias Encefálicas/complicações , Feminino , Glioma/complicações , Humanos , Ventrículos Laterais/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Modelos de Riscos Proporcionais , Convulsões/etiologia
3.
Nature ; 569(7758): 672-678, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31092925

RESUMO

Autonomic nerve fibres in the tumour microenvironment regulate cancer initiation and dissemination, but how nerves emerge in tumours is currently unknown. Here we show that neural progenitors from the central nervous system that express doublecortin (DCX+) infiltrate prostate tumours and metastases, in which they initiate neurogenesis. In mouse models of prostate cancer, oscillations of DCX+ neural progenitors in the subventricular zone-a neurogenic area of the central nervous system-are associated with disruption of the blood-brain barrier, and with the egress of DCX+ cells into the circulation. These cells then infiltrate and reside in the tumour, and can generate new adrenergic neurons. Selective genetic depletion of DCX+ cells inhibits the early phases of tumour development in our mouse models of prostate cancer, whereas transplantation of DCX+ neural progenitors promotes tumour growth and metastasis. In humans, the density of DCX+ neural progenitors is strongly associated with the aggressiveness and recurrence of prostate adenocarcinoma. These results reveal a unique crosstalk between the central nervous system and prostate tumours, and indicate neural targets for the treatment of cancer.


Assuntos
Sistema Nervoso Central/patologia , Células-Tronco Neurais/patologia , Neurogênese , Neoplasias da Próstata/patologia , Adenocarcinoma/patologia , Neurônios Adrenérgicos/patologia , Animais , Carcinogênese , Diferenciação Celular , Modelos Animais de Doenças , Genes myc , Humanos , Ventrículos Laterais/patologia , Masculino , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Células-Tronco Neurais/metabolismo , Neuropeptídeos/metabolismo , Bulbo Olfatório/patologia , Prognóstico
4.
Mult Scler Relat Disord ; 31: 93-96, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30953954

RESUMO

BACKGROUND: A periventricular gradient of normal appearing white matter (NAWM) damage has been described in multiple sclerosis (MS), including subjects with clinically isolated syndrome (CIS). The pathological mechanisms underlying this gradient is not currently understood. METHODS: 34 CIS subjects were enrolled and underwent cerebrospinal fluid oligo-clonal bands (CSF-OCB) evaluation. Moreover, all CIS subjects and 24 healthy controls underwent a brain MRI scan. Diffusion weighted imaging was used to compute mean diffusivity (MD) values in periventricular and deep NAWM for all groups. RESULTS: CSF-OCB were present in 24 CIS subjects (CSF-OCB+) out of 34 tested. Periventricular NAWM MD values were significantly higher in CIS subjects with than in those without CSF-OCB (0.78 ± 0.06 mm3/10-3 vs. 0.72 ± 0.06 mm3/10-3; p = 0.01), while there was no difference between groups in deep NAWM MD values. The periventricular gradient of damage, expressed in z score based on healthy controls data, was more marked in CSF-OCB+ than in CSF-OCB- (0.65 ± 0.05 vs. 0.17 ± 0.04 p < 0.001). There was no difference in periventricular lesion load between the two groups. CONCLUSIONS: In CIS, the presence of CSF-OCB is associated with the severity of periventricular NAWM damage gradient. Intrathecal inflammation could play a role in NAWM damage distribution.


Assuntos
Doenças Desmielinizantes/patologia , Ventrículos Laterais/patologia , Esclerose Múltipla/patologia , Bandas Oligoclonais/líquido cefalorraquidiano , Substância Branca/patologia , Adulto , Doenças Desmielinizantes/líquido cefalorraquidiano , Doenças Desmielinizantes/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Ventrículos Laterais/diagnóstico por imagem , Masculino , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
5.
Bull Exp Biol Med ; 166(6): 793-796, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31028587

RESUMO

One of the most common models of sporadic form of Alzheimer's disease is injection of streptozotocin into the lateral ventricles of rat brain. In 3 months after this injection, an increase in the expression of astroglia in the corpus callosum and a decrease in the thickness of the corpus callosum and intensity of its staining with luxol fast blue were observed. This can reflect a decrease in the content of myelinated fibers. In layer V of the sensorimotor cortex, intensive degeneration of neurons was revealed. The lateral ventricles were significantly enlarged and the expression of PSA-NCAM protein, a marker of immature neurons, was reduced in subventricular zone, which can be associated with disturbed neurogenesi.


Assuntos
Doença de Alzheimer/patologia , Astrócitos/patologia , Corpo Caloso/patologia , Ventrículos Laterais/patologia , Fibras Nervosas Mielinizadas/patologia , Córtex Sensório-Motor/patologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Animais , Astrócitos/metabolismo , Biomarcadores/metabolismo , Corpo Caloso/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Indóis , Injeções Intraventriculares , Ventrículos Laterais/metabolismo , Masculino , Fibras Nervosas Mielinizadas/metabolismo , Molécula L1 de Adesão de Célula Nervosa/genética , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Ratos , Ratos Wistar , Córtex Sensório-Motor/metabolismo , Ácidos Siálicos/genética , Ácidos Siálicos/metabolismo , Técnicas Estereotáxicas , Estreptozocina/administração & dosagem
6.
Radiat Oncol ; 14(1): 37, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30832691

RESUMO

BACKGROUND: Subventricular zone (SVZ) involvement is associated with a dismal prognosis in patients with glioblastoma multiforme (GBM). Dual-time point (dtp) O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET/CT (PET) may be a time- and cost-effective alternative to dynamic FET PET, but its prognostic value, particularly with respect to SVZ involvement, is unknown. METHODS: Thirty-five patients had two scans 5-15 and 50-60 min after i.v. FET injection to define tumor volumes and SVZ involvement before starting radiotherapy. Associations between clinical progression markers, MRI- and dtp FET PET-based tumor volumes, or SVZ involvement and progression-free (PFS) and overall survival (OS) were assessed in univariable and multivariable analyses. RESULTS: The extent of resection was not related to outcomes. Albeit non-significant, dtp FET PET detected more SVZ infiltration than MRI (60% vs. 51%, p = 0.25) and was significantly associated with poor survival (p < 0.03), but PET-T1-Gad volumes were larger in this group (p < 0.002). Survival was shorter in patients with larger MRI tumor volumes, larger PET tumor volumes, and worse Karnofsky performance status (KPS), with fused PET-T1-Gad and KPS significant in multivariable analysis (p < 0.03). Uptake kinetics was not associated with treatment outcomes. CONCLUSIONS: FET PET-based tumor volumes may be useful for predicting worse prognosis glioblastoma. Although the presence of SVZ infiltration is linked to higher PET/MRI-based tumor volumes, the independent value of dtp FET PET parameters and SVZ infiltration as prognostic markers pre-irradiation has not been confirmed.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/diagnóstico por imagem , Ventrículos Laterais/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Feminino , Radioisótopos de Flúor , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Estimativa de Kaplan-Meier , Ventrículos Laterais/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Carga Tumoral
7.
J Forensic Sci ; 64(5): 1548-1550, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30791098

RESUMO

Primary intraventricular hemorrhage (PIVH) is a rare type of stroke defined as bleeding within the ventricles of the brain without any associated parenchymal hemorrhage. Here, we reported two cases of sudden death due to PIVH. One of the patients was found dead under a highway bridge without witnesses, and the other patient was hospitalized with hemorrhage in the ventricular system, as revealed by a head computed tomography scan. In these two patients, autopsy and macroscopic examination only showed hemorrhages in the ventricular system without any traumatic brain injury or other intraparenchymal hemorrhage. The sources of bleeding for both patients were ultimately confirmed as ruptured brain arteriovenous malformations located in the subventricular zone. We reported these cases to broaden our understanding of sudden death associated with PIVH, especially when caused by brain arteriovenous malformation. We also summarized the essential details of the diagnoses and available technical methods for PIVH cases.


Assuntos
Hemorragia Cerebral/patologia , Morte Súbita/etiologia , Malformações Arteriovenosas Intracranianas/patologia , Actinas/metabolismo , Adulto , Humanos , Malformações Arteriovenosas Intracranianas/metabolismo , Ventrículos Laterais/patologia , Masculino , Miócitos de Músculo Liso/metabolismo , Ruptura Espontânea
8.
Psychiatry Res ; 277: 45-51, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30808608

RESUMO

INTRODUCTION: Abnormalities in the corpus callosum (CC) and the lateral ventricles (LV) are hallmark features of schizophrenia. These abnormalities have been reported in chronic and in first episode schizophrenia (FESZ). Here we explore further associations between CC and LV in FESZ using diffusion tensor imaging (DTI). METHODS: . Sixteen FESZ patients and 16 healthy controls (HC), matched on age, gender, and handedness participated in the study. Diffusion and structural imaging scans were acquired on a 3T GE Signa magnet. Volumetric measures for LV and DTI measures for five CC subdivisions were completed in both groups. In addition, two-tensor tractography, the latter corrected for free-water (FAt), was completed for CC. Correlations between LV and DTI measures of the CC were examined in both groups, while correlations between DTI and clinical measures were examined in only FESZ. RESULTS: Results from two-tensor tractography demonstrated decreased FAt and increased trace and radial diffusivity (RDt) in the five CC subdivisions in FESZ compared to HC. Central CC diffusion measures in FESZ were significantly correlated with volume of the LV, i.e., decreased FAt values were associated with larger LV volume, while increased RDt and trace values were associated with larger LV volume. In controls, correlations were also significant, but they were in the opposite direction from FESZ. In addition, decreased FAt in FESZ was associated with more positive symptoms. DISCUSSION: Partial volume corrected FAt, RDt, and trace abnormalities in the CC in FESZ suggest possible de- or dys-myelination, or changes in axonal diameters, all compatible with neurodevelopmental theories of schizophrenia. Correlational findings between the volume of LV and diffusion measures in FESZ reinforce the concept of a link between abnormalities in the LV and CC in early stages of schizophrenia and are also compatible with neurodevelopmental abnormalities in this population.


Assuntos
Corpo Caloso/diagnóstico por imagem , Imagem de Tensor de Difusão , Ventrículos Laterais/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Adulto , Corpo Caloso/patologia , Feminino , Humanos , Ventrículos Laterais/patologia , Masculino , Esquizofrenia/patologia , Substância Branca/diagnóstico por imagem , Adulto Jovem
9.
Bull Exp Biol Med ; 166(3): 317-320, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30627909

RESUMO

The in vitro and in vivo models of ethanol-induced neurodegeneration were used to evaluate the content and functional activity of various types of regeneration-competent cells in subventricular zone of the cerebral hemispheres in C57Bl/6JY mice. In nervous tissue culture, ethanol (65 mM) produced no effect on formation of neurospheres. When administered per os in a daily dose of 3 g/kg for 8 weeks, ethanol produced no effect on the number of neural CFU in situ. In both cases, ethanol reduced proliferative activity of neural CFU. Long-term administration of ethanol in vivo suppressed differentiation of neural stem cells and decreased the number of committed precursors (neural cluster-forming units) in the subventricular zone of cerebral hemispheres. In vitro application of ethanol stimulated secretion of humoral growth factors by the cluster-forming neural glial cells. In contrast, in vivo administration of ethanol suppressed this secretion.


Assuntos
Alcoolismo/patologia , Cérebro/efeitos dos fármacos , Etanol/farmacologia , Ventrículos Laterais/efeitos dos fármacos , Doenças Neurodegenerativas/patologia , Neurônios/efeitos dos fármacos , Alcoolismo/metabolismo , Animais , Contagem de Células , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cérebro/metabolismo , Cérebro/patologia , Cérebro/fisiopatologia , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intercelular/agonistas , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Ventrículos Laterais/metabolismo , Ventrículos Laterais/patologia , Ventrículos Laterais/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/patologia , Doenças Neurodegenerativas/metabolismo , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Neuroglia/patologia , Neurônios/patologia , Cultura Primária de Células , Esferoides Celulares/efeitos dos fármacos
10.
Genes Brain Behav ; 18(4): e12540, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30430717

RESUMO

Schizophrenia is a hereditary disease that approximately 1% of the worldwide population develops. Many studies have investigated possible underlying genes related to schizophrenia. Recently, clinical studies suggested sterol regulatory element-binding protein (SREBP) as a susceptibility gene in patients with schizophrenia. SREBP controls cellular lipid homeostasis by three isoforms: SREBP-1a, SREBP-1c and SREBP-2. This study used SREBP-1c knockout (KO) mice to examine whether a deficiency in SREBP-1c would affect their emotional and psychiatric behaviors. Altered mRNA expression in genes downstream from SREBP-1c was confirmed in the brains of SREBP-1c KO mice. Schizophrenia-like behavior, including hyperactivity during the dark phase, depressive-like behavior, aggressive behavior and deficits in social interaction and prepulse inhibition, was observed in SREBP-1c KO mice. Furthermore, increased volume of the lateral ventricle was detected in SREBP-1c KO mice. The mRNA levels of several γ-aminobutyric acid (GABA)-receptor subtypes and/or glutamic acid decarboxylase 65/67 decreased in the hippocampus and medial prefrontal cortex of SREBP-1c KO mice. Thus, SREBP-1c deficiency may contribute to enlargement of the lateral ventricle and development of schizophrenia-like behaviors and be associated with altered GABAergic transmission.


Assuntos
Esquizofrenia/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Animais , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/metabolismo , Hipocampo/metabolismo , Ventrículos Laterais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/metabolismo , Receptores de GABA/genética , Receptores de GABA/metabolismo , Esquizofrenia/metabolismo , Esquizofrenia/fisiopatologia , Proteína de Ligação a Elemento Regulador de Esterol 1/deficiência
11.
Oncogene ; 38(1): 73-87, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30082913

RESUMO

Primary glioblastoma is the most frequent human brain tumor in adults and is generally fatal due to tumor recurrence. We previously demonstrated that glioblastoma-initiating cells invade the subventricular zones and promote their radio-resistance in response to the local release of the CXCL12 chemokine. In this work, we show that the mitotic Aurora A kinase (AurA) is activated through the CXCL12-CXCR4 pathway in an ERK1/2-dependent manner. Moreover, the CXCL12-ERK1/2 signaling induces the expression of Ajuba, the main cofactor of AurA, which allows the auto-phosphorylation of AurA.We show that AurA contributes to glioblastoma cell survival, radio-resistance, self-renewal, and proliferation regardless of the exogenous stimulation with CXCL12. On the other hand, AurA triggers the CXCL12-mediated migration of glioblastoma cells in vitro as well as the invasion of the subventricular zone in xenograft experiments. Moreover, AurA regulates cytoskeletal proteins (i.e., Actin and Vimentin) and favors the pro-migratory activity of the Rho-GTPase CDC42 in response to CXCL12. Altogether, these results show that AurA, a well-known kinase of the mitotic machinery, may play alternative roles in human glioblastoma according to the CXCL12 concentration.


Assuntos
Aurora Quinase A/fisiologia , Neoplasias Encefálicas/enzimologia , Quimiocina CXCL12/fisiologia , Glioblastoma/enzimologia , Proteínas de Neoplasias/fisiologia , Animais , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular , Quimiocina CXCL12/farmacologia , Ativação Enzimática , Glioblastoma/patologia , Xenoenxertos , Humanos , Proteínas com Domínio LIM/biossíntese , Proteínas com Domínio LIM/genética , Ventrículos Laterais/patologia , Sistema de Sinalização das MAP Quinases , Camundongos , Invasividade Neoplásica , Fosforilação , Processamento de Proteína Pós-Traducional , Receptores CXCR4/fisiologia , Transdução de Sinais
12.
J Neurosurg Sci ; 63(5): 581-587, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29205011

RESUMO

INTRODUCTION: The clinical and molecular correlates of glioblastomas (GBMs) contacting the subventricular zone (SVZ+ GBM) are unknown. This work aimed to reveal any such correlates that may help explain their increased GBM malignancy. EVIDENCE ACQUISITION: A meta-analysis was, therefore, conducted to assess whether tumor's MGMT promoter methylation status, isocitrate dehydrogenase (IDH) mutation status, volume, and extent of resection as well as patients' age at diagnosis and preoperative Karnofsky performance status score (KPS) correlate with SVZ contact by GBM. In addition, available imaging of GBM patients in The Cancer Imaging Archive was assessed for SVZ contact and their corresponding clinical and molecular variables were obtained through The Cancer Genome Atlas (TCGA) database. EVIDENCE SYNTHESIS: Twenty-one studies were identified through PubMed and EMBASE database search. This review included 257 patients identified from the TCIA/TCGA database. MGMT promoter methylation status (summary odds ratio [OD], 1.18 [0.84-1.66], P=0.34), IDH mutation status (OD: 0.63 [0.20-1.99], P=0.43), and patients' age of diagnosis (summary mean difference, MD, 0.10 years [-1.85, 2.05], P=0.92) did not associated with SVZ contact of the GBM. However, SVZ+ GBMs were significantly larger than SVZ- GBMs (MD: 17.3 cm3 [8.70-25.8], P<0.0001). SVZ+ GBM patients had lower KPS scores (MD: -3.33 [-5.31-(-1.35)], P=0.001) and were half as likely to receive a gross total resection (OD: 0.50 [0.40-0.64], P<0.00001). CONCLUSIONS: Additional, large studies that rigorously control for all the known clinical and molecular prognosticators, especially extent of resection and preoperative KPS scores, are needed to evaluate whether SVZ contact by GBM independently influences survival.


Assuntos
Neoplasias Encefálicas/genética , Glioblastoma/genética , Ventrículos Laterais/patologia , Mutação/genética , Adulto , Neoplasias Encefálicas/cirurgia , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Feminino , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas/genética , Proteínas Supressoras de Tumor/genética
13.
Br J Neurosurg ; 33(5): 581-583, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28992740

RESUMO

Subependymomas are rare benign tumours arising from subependymal glial precursors that usually remain asymptomatic or may present due to obstruction of cerebrospinal fluid pathways. We describe the first report of intraventricular haemorrhage from subependymoma and cavernous-like malformation collision tumour in a 74-year-old male presented with an impaired level of consciousness.


Assuntos
Malformações Vasculares do Sistema Nervoso Central/complicações , Neoplasias do Ventrículo Cerebral/complicações , Glioma Subependimal/complicações , Idoso , Hemorragia Cerebral/complicações , Hemorragia Cerebral/patologia , Neoplasias do Ventrículo Cerebral/patologia , Neoplasias do Ventrículo Cerebral/cirurgia , Craniotomia/métodos , Glioma Subependimal/cirurgia , Humanos , Ventrículos Laterais/patologia , Imagem por Ressonância Magnética , Masculino , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Inconsciência/etiologia
14.
AJNR Am J Neuroradiol ; 39(12): 2237-2242, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30467212

RESUMO

BACKGROUND AND PURPOSE: The assessment of brain atrophy in a clinical routine is not performed routinely in multiple sclerosis. Our aim was to determine the feasibility of brain atrophy measurement and its association with disability progression in patients with MS followed in a clinical routine for 5 years. MATERIALS AND METHODS: A total of 1815 subjects, 1514 with MS and 137 with clinically isolated syndrome and 164 healthy individuals, were collected retrospectively. Of 11,794 MR imaging brain scans included in the analysis, 8423 MRIs were performed on a 3T, and 3371 MRIs, on a 1.5T scanner. All patients underwent 3D T1WI and T2-FLAIR examinations at all time points of the study. Whole-brain volume changes were measured by percentage brain volume change/normalized brain volume change using SIENA/SIENAX on 3D T1WI and percentage lateral ventricle volume change using NeuroSTREAM on T2-FLAIR. RESULTS: Percentage brain volume change failed in 36.7% of the subjects; percentage normalized brain volume change, in 19.2%; and percentage lateral ventricle volume change, in 3.3% because of protocol changes, poor scan quality, artifacts, and anatomic variations. Annualized brain volume changes were significantly different between those with MS and healthy individuals for percentage brain volume change (P < .001), percentage normalized brain volume change (P = .002), and percentage lateral ventricle volume change (P = .01). In patients with MS, mixed-effects model analysis showed that disability progression was associated with a 21.9% annualized decrease in percentage brain volume change (P < .001) and normalized brain volume (P = .002) and a 33% increase in lateral ventricle volume (P = .004). CONCLUSIONS: All brain volume measures differentiated MS and healthy individuals and were associated with disability progression, but the lateral ventricle volume assessment was the most feasible.


Assuntos
Ventrículos Laterais/patologia , Esclerose Múltipla/patologia , Adulto , Atrofia/complicações , Atrofia/diagnóstico por imagem , Atrofia/patologia , Progressão da Doença , Feminino , Humanos , Ventrículos Laterais/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Neuroimagem/métodos , Estudos Retrospectivos
15.
Transl Psychiatry ; 8(1): 254, 2018 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-30487578

RESUMO

Subcortical structures may have an important role in the pathophysiology of psychosis. Our recent mega-analysis of structural magnetic resonance imaging (MRI) data has reported subcortical volumetric and lateralization alterations in chronic schizophrenia, including leftward asymmetric increases in pallidal volume. The question remains, however, whether these characteristics may represent vulnerability to the development of psychosis or whether they are epiphenomena caused by exposure to medication or illness chronicity. Subclinical psychotic experiences (SPEs) occur in some adolescents in the general population and increase the odds of developing psychosis in young adulthood. Investigations into the association between SPEs and MRI-measured volumes of subcortical structures in the general adolescent population would clarify the issue. Here, we collected structural MRI data in a subsample (10.5-13.3 years old) of a large-scale population-based cohort and explored subcortical volume and lateralization alterations related to SPEs (N = 203). Adolescents with SPEs demonstrated significant volumetric increases in the left hippocampus, right caudate, and right lateral ventricle, as well as a marginally significant increase in the left pallidum. Furthermore, adolescents with SPEs showed significantly more leftward laterality of pallidal volume than individuals without SPEs, which replicates our mega-analysis findings in chronic schizophrenia. We suggest that leftward asymmetries in pallidal volume already present in early adolescence may underlie the premorbid predisposition for developing psychosis in later life.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Núcleo Caudado/patologia , Globo Pálido/patologia , Hipocampo/patologia , Ventrículos Laterais/patologia , Transtornos Psicóticos/patologia , Adolescente , Criança , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Transtornos Psicóticos/diagnóstico por imagem
16.
Pediatr Neurosurg ; 53(6): 401-406, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30391955

RESUMO

Choroid plexus papilloma (CPP) is a rare benign tumor of the central nervous system. Bilateral lateral ventricle CPP is extremely uncommon. In this case report, we described a case of bilateral lateral ventricle CPP in a 4-month-old female patient conceived by in vitro fertilization (IVF). Neurological examination and imaging were performed. In neurological examination, meningeal irritation signs and sunset phenomenon were positive. Brain computed tomography (CT) and magnetic resonance imaging (MRI) displayed masses located in the trigone of the bilateral lateral ventricle with hydrocephalus. Contrast-enhanced MRI showed intense homogeneous enhancement. The diagnoses of bilateral lateral ventricle CPP related to hydrocephalus and extravasation of cerebrospinal fluid (CSF) were made. Repeated surgical procedures via parietotemporal craniotomy were performed, and the diagnosis was confirmed by histopathology examination. The patient presented with delayed development during a follow-up period of 1 year. In conclusion, imaging is an effective approach of investigation. CPP could be highly suspected according to the features of hydrocephalus, lobulated appearance, and homogeneous enhancement on imaging. Total surgical removal is a valid curative method for CPP.


Assuntos
Neoplasias do Ventrículo Cerebral/cirurgia , Ventrículos Laterais/diagnóstico por imagem , Ventrículos Laterais/patologia , Papiloma do Plexo Corióideo/diagnóstico por imagem , Papiloma do Plexo Corióideo/patologia , Neoplasias do Ventrículo Cerebral/patologia , Feminino , Fertilização In Vitro , Humanos , Hidrocefalia/líquido cefalorraquidiano , Hidrocefalia/patologia , Hidrocefalia/cirurgia , Lactente , Ventrículos Laterais/cirurgia , Imagem por Ressonância Magnética , Papiloma do Plexo Corióideo/cirurgia , Tomografia Computadorizada por Raios X
17.
Br J Neurosurg ; 32(6): 614-618, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30282472

RESUMO

BACKGROUND: It is suspected that infiltration of stem cell areas with high-grade glioma (HGG) generates a population that compromises treatment results and survival. In this prospective study we set to assess the prognostic value of the proximity of the contrast-enhancing lesion (CEL) on MRI to the subventricular zone (SVZ) and the expression of CXCR4 and nestin as potential factors in the stem cell migration pathway. METHOD: All patients diagnosed with high-grade glioma over a three-year period from a single institution were enrolled in this prospective study. Based on MRI preoperative findings, the patients were classified into 4 Groups (I-IV) according to the proximity of the CEL on MRI to the SVZ. Histological samples were assessed with immunohistochemistry for nestin and CXCR4. Classification into groups and the presence of nestin and CXCR4 were evaluated as predictive factors for overall (OS) and progression free survival (PFS). RESULTS: Fourty patients were included in the study. In multivariate analysis, Groups II, III and IV predicted longer OS in comparison to group I (p = 0.01; p < 0.01; p < 0.01 respectively) and group III and IV predicted longer OS in comparison to group II (p < 0.01; p = 0.04 respectively). Group III predicted longer PFS than group I and II (p = 0.01; p < 0.01 respectively). The expression rates of CXCR-4 and nestin could not predict OS or PFS. CONCLUSIONS: In our study the classification according to the proximity of the contrast enhancing part of the lesion and the SVZ proved to be prognostically significant for both OS and PFS. Presence of CXCR4 or nestin was not predictive for OS or PFS.


Assuntos
Neoplasias Encefálicas/mortalidade , Glioma/mortalidade , Nestina/metabolismo , Receptores CXCR4/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Intervalo Livre de Doença , Feminino , Glioma/patologia , Glioma/cirurgia , Grécia/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Ventrículos Laterais/patologia , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/patologia , Procedimentos Neurocirúrgicos/mortalidade , Prognóstico , Estudos Prospectivos
18.
BMB Rep ; 51(10): 481-483, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30269745

RESUMO

Glioblastoma (GBM) is the most common and aggressive form of human adult brain malignancy. The identification of the cell of origin harboring cancer-driver mutations is the fundamental issue for understanding the nature of GBM and developing the effective therapeutic target. It has been a long-term hypothesis that neural stem cells in the subventricular zone (SVZ) might be the origin-of-cells in human glioblastoma since they are known to have life-long proliferative activity and acquire somatic mutations. However, the cell of origin for GBM remains controversial due to lack of direct evidence thereof in human GBM. Our recent study using various sequencing techniques in triple matched samples such as tumor-free SVZ, tumor, and normal tissues from human patients identified the clonal relationship of driver mutations between GBM and tumor-free SVZ harboring neural stem cells (NSCs). Tumor-free SVZ tissue away from the tumor contained low-level GBM driver mutations (as low as 1% allelic frequency) that were found in the dominant clones in its matching tumors. Moreover, via single-cell sequencing and microdissection, it was discovered that astrocyte-like NSCs accumulating driver mutations evolved into GBM with clonal expansion. Furthermore, mutagenesis of cancer-driving genes of NSCs in mice leads to migration of mutant cells from SVZ to distant brain and development of high-grade glioma through the aberrant growth of oligodendrocyte precursor lineage. Altogether, the present study provides the first direct evidence that NSCs in human SVZ is the cell of origin that develops the driver mutations of GBM. [BMB Reports 2018; 51(10): 481-483].


Assuntos
Glioblastoma/genética , Glioblastoma/patologia , Mutação/genética , Astrócitos/patologia , Humanos , Ventrículos Laterais/patologia , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia
19.
Neurobiol Aging ; 72: 40-52, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30205359

RESUMO

There is vast knowledge on pathogenic mechanisms in Alzheimer's disease but very little on means by which the brain protects itself from disease. A major candidate in providing neuroprotection is the resident brain neural precursor/stem cell (NPC) pool. Transplanted NPCs possess powerful immune-modulatory and trophic properties in vivo and in vitro, underscoring the question whether resident brain NPCs have any role in regulating disease pathology in Alzheimer's disease, and particularly whether they fail to protect the brain from degeneration. To evaluate brain NPC function in relation to disease pathology, we first characterized the pathological properties of 5xFAD transgenic mouse model of Alzheimer's disease at different ages. We found that age 7 months is a critical time point of heavy amyloid deposition and gliosis but before neurodegeneration and a normal basal rate of NPC turnover in the subventricular zone (SVZ) of 5xFAD mice as compared to wild-type mice. Analysis of NPC functional properties showed that despite preserved rate of turnover, there was substantial SVZ NPC dysfunction as indicated by both ex vivo and in vivo assays. Freshly isolated NPCs from 7-month-old 5xFAD mice exhibited reduced expansion rate and diminished immune-modulatory and trophic properties. Moreover, there was slowed recovery of SVZ NPCs after cytosine-arabinoside insult and markedly reduced migratory response following a lysolecithin-induced lesion in the corpus callosum in vivo. Importantly, these functions were fully preserved in 2-month-old 5xFAD mice, a time point before Alzheimer's disease-specific pathological changes. There was reduced expression of key genes involved in NPC proliferative and migratory response in NPCs derived from 7-month-old 5xFAD mice. The dysfunctional properties and downregulation of gene expression were reversible in NPCs derived from 7-month-old 5xFAD mice following in vitro expansion and were reproduced in wild-type NPC by addition of amyloid beta peptide. Thus, there is age-dependent acquired NPC dysfunction, with loss of immune-modulatory and neurotrophic properties, which is induced by the pathological Alzheimer's brain environment at a critical time point before neurodegeneration. We suggest that failure of resident NPC to provide tissue support may be involved in promoting neurodegeneration.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Regulação para Baixo , Ventrículos Laterais/patologia , Células-Tronco Neurais/metabolismo , Fatores Etários , Doença de Alzheimer/genética , Doença de Alzheimer/imunologia , Doença de Alzheimer/metabolismo , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
20.
Pharmazie ; 73(10): 585-588, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30223922

RESUMO

Recent studies have shown that telmisartan (TMS) is effective for the protection against ischemia/brain damage in rat models. However, the specific underlying mechanism is poorly understood. In line with previous results, our data showed that TMS improves CBF and physiological variables, including pH, pCO2, pO2. Through CD31 immunofluorescence staining, reduction of blood vessel density was found in MCAO group, but TMS treatment could enhance the cerebral vascular density in the ischemic area. Meanwhile, TMS treatment could enhance the number of BrdU/lectin double-positive cells. Furthermore, the reduction of nestin-positive cells was identified in the brain of MCAO rats, while the number of nestin-positive cells was significantly increased after TMS administration. Furthermore, the expression of ERS-related proteins, including GRP78, CHOP/GADD153, Caspase12 was increased after MCAO, but was decreased after administration of TMS, thereby enhancing angiogenesis and neuron regeneration.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Telmisartan/farmacologia , Animais , Apoptose/efeitos dos fármacos , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Encéfalo/patologia , Caspase 12/metabolismo , Proteínas de Choque Térmico/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Ventrículos Laterais/efeitos dos fármacos , Ventrículos Laterais/metabolismo , Ventrículos Laterais/patologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Transcrição CHOP/metabolismo
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