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1.
Isr Med Assoc J ; 22(1): 27-31, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31927802

RESUMO

BACKGROUND: Congenital heart defects (CHD) may be associated with neurodevelopmental abnormalities mainly due to brain hypoperfusion. This defect is attributed to the major cardiac operations these children underwent, but also to hemodynamic instability during fetal life. Advances in imaging techniques have identified changes in brain magnetic resonance imaging (MRI)in children with CHD. OBJECTIVES: To examine the correlation between CHD and brain injury using fetal brain MRI. METHODS: We evaluated 46 fetuses diagnosed with CHD who underwent brain MRI. CHD was classified according to in situs anomalies, 4 chamber view (4CV), outflow tracts, arches, and veins as well as cyanotic or complex CHD. We compared MRI results of different classes of CHD and CHD fetuses to a control group of 113 healthy brain MRI examinations. RESULTS: No significant differences were found in brain pathologies among different classifications of CHD. The anteroposterior percentile of the vermis was significantly smaller in fetuses with abnormal 4CV. A significantly higher biparietal diameter was found in fetuses with abnormal arches. A significantly smaller transcerebellar diameter was found in fetuses with abnormal veins. Compared to the control group, significant differences were found in overall brain pathology in cortex abnormalities and in extra axial findings in the study group. Significantly higher rates of overall brain pathologies, ventricle pathologies, cortex pathologies, and biometrical parameters were found in the cyanotic group compared to the complex group and to the control group. CONCLUSIONS: Fetuses with CHD demonstrate findings in brain MRI that suggest an in utero pathogenesis of the neurological and cognitive anomalies found during child development.


Assuntos
Lesões Encefálicas/embriologia , Feto/diagnóstico por imagem , Cardiopatias Congênitas/etiologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/embriologia , Encéfalo/patologia , Lesões Encefálicas/complicações , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/patologia , Estudos de Casos e Controles , Ecocardiografia , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Neuroimagem , Gravidez , Diagnóstico Pré-Natal/métodos
2.
Adv Exp Med Biol ; 1232: 47-53, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893393

RESUMO

Cerebrovascular reactivity (CVR) is a compensatory mechanism where blood vessels dilate in response to a vasodilatory stimulus, and is a biomarker of vascular reserve and microvascular health. Impaired CVR indicates microvascular hemodynamic dysfunction, which is implicated in traumatic brain injury (TBI) and associated with long-term neurological deficiency. Recently we have shown that anodal transcranial direct current stimulation (tDCS) caused prolonged dilatation of cerebral arterioles that increased brain microvascular flow and tissue oxygenation in traumatized mouse brain and was associated with neurologic improvement. Here we evaluate the effects of tDCS on impaired CVR and microvascular cerebral blood flow (mCBF) regulation after TBI. TBI was induced in mice by controlled cortical impact (CCI). Cortical microvascular tone, mCBF, and tissue oxygen supply (by nicotinamide adenine dinucleotide, NADH) were measured by two-photon laser scanning microscopy before and after anodal tDCS (0.1 mA/15 min). CVR and mCBF regulation were evaluated by measuring changes in arteriolar diameters and NADH during hypercapnia test before and after tDCS. Transient hypercapnia was induced by 60-s increase of CO2 concentration in the inhalation mixture to 10%. As previously, anodal tDCS dilated arterioles which increased arteriolar blood flow volume that led to an increase in capillary flow velocity and the number of functioning capillaries, thereby improving tissue oxygenation in both traumatized and sham animals. In sham mice, transient hypercapnia caused transient dilatation of cerebral arterioles with constant NADH, reflecting intact CVR and mCBF regulation. In TBI animals, arteriolar dilatation response to hypercapnia was diminished while the NADH level increased (tissue oxygen supply decreased), reflecting impaired CVR and mCBF regulation. Anodal tDCS enhanced reactivity in parenchymal arterioles in both groups (especially in TBI mice) and restored CVR thereby prevented the reduction in tissue oxygen supply during hypercapnia. CVR has been shown to be related to nitric oxide elevation due to nitric oxide synthases activation, which can be sensitive to the electrical field induced by tDCS.


Assuntos
Lesões Encefálicas Traumáticas , Circulação Cerebrovascular , Estimulação Transcraniana por Corrente Contínua , Animais , Encéfalo/patologia , Lesões Encefálicas Traumáticas/terapia , Circulação Cerebrovascular/fisiologia , Hipercapnia , Camundongos
3.
Chemosphere ; 239: 124758, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31514009

RESUMO

Trace elements such as copper (Cu) and arsenic (As) are two of the major contaminants and well-known inducers of cognitive deficits and neurobehavioral changes. This study evaluated the immunotoxicity of their individual or combined exposure on different brain regions in chickens. Consequently, nuclear damage and organelle lesions, especially mitochondria were observed under Cu or/and As stress, in which positive regulation of key proteins, dynamin-related protein 1 (Drp1), Cytochrome C (Cyt c), BCL2-associated X (Bax), Caspases 3 and P53 was detected by qRCR and Western blot analyses, indicating disturbed mitochondrial dynamic equilibrium and apoptosis execution. In addition, qRCR analysis confirmed the involvement of cytokines secreted by different populations of helper T cells, indicative of cellular immunity. Gene expression studies showed marked up regulation of Th1/Th17 cytokines along with heat shock protein (HSP) 70, a synergism was noted in co-administration group. Interesting, lower apoptosis index was noted in brainstem compared to cerebrum and cerebellum. An intense immunosuppression and heat shock response against Cu or/and As was also seen in cerebrum and cerebellum but not in brainstem. In conclusion, our study suggests a synergistic neurotoxicity in chickens under Cu and As exposure. These findings provide a basic understanding of mitochondrial abnormality-initiated neuropathology in response to environmental pollutant mixtures, suggesting an adaptive response to the frangibility of the central nerve system.


Assuntos
Arsenitos/toxicidade , Encéfalo/efeitos dos fármacos , Galinhas/imunologia , Cobre/toxicidade , Tolerância Imunológica/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Encéfalo/patologia , Poluentes Ambientais/toxicidade , Resposta ao Choque Térmico/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Masculino , Dinâmica Mitocondrial/efeitos dos fármacos
4.
Life Sci ; 241: 117154, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31857087

RESUMO

AIM: Insulin resistance and neuroinflammation play roles in Alzheimer's (AD) etiology. Insulin receptors (IR) are developmentally expressed in neurons as well as astrocytes. Moreover, prolonged stress can induce brain insulin resistance and astrogliosis. Also, prenatal stress could advance AD-related abnormalities in a transgenic model of AD. Besides, postnatal maternal care (PMC) has antagonistic effects on prenatal stress (PS)-induced neuronal and immunological malfunctions. Using an icv-STZ subclinical model of sAD, we assessed PS and/or abnormal PMC impacts on advancing sAD-like pathology in adult male rats. We also sought astrocyte- and/or neuron-oriented change in central insulin programming. MAIN METHODS: Pregnant rats were exposed to PS. Thereafter, a group of pups was fostered onto unstressed mothers and the others remained intact. Real-time RT-PCR- for hippocampal IR, Tau, and ChAT transcripts- and immunohistochemistry analysis- for GFAP+ astrocytes- were performed at the first- and forth-postnatal-week, respectively. The other animals received icv-STZ0.5 mg/kg in adulthood and subjected to cognitive tests, molecular, and histological experiments at appropriate time-point post-injection. KEY FINDINGS: PS could advance sAD-related symptoms in icv-STZ-treated animals. PS changed expression levels of hippocampal IR in one-week-old and 5.5-month-old offspring. PS could worsen cognitive, molecular and histological impairments of icv-STZ. Adequate PMC prevented some destructive effects of PS. SIGNIFICANCE: PS can potentially change central insulin programming and induce long-lasting astrogliosis in rat hippocampus. PS-related cognitive and histological pathologies can rescue by PMC probably via IR-dependent pathways. Astrocyte involvement in AD-like neuropathology observed in stressed-animals needs more detailed investigations.


Assuntos
Doença de Alzheimer/patologia , Comportamento Animal , Modelos Animais de Doenças , Resistência à Insulina , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Estreptozocina/toxicidade , Estresse Psicológico/complicações , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Animais , Animais Recém-Nascidos , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Infusões Intraventriculares , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Gravidez , Ratos , Ratos Wistar , Receptor de Insulina/metabolismo , Transdução de Sinais , Estreptozocina/administração & dosagem
5.
Prax Kinderpsychol Kinderpsychiatr ; 68(7): 575-591, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31711395

RESUMO

Early Life Stress Stress and daily hassles are a normal part of day-to day-life. The amount of control that is experienced strongly contributes to resilience and coping. Children very frequently do not experience control over the stressors within their lives. Starting from pregnancy, they are subjected - via the maternal endocrine system - to a variety of stressors ranging from normal stress regarding the transition to parenthood to maternal abuse or torture. This article collects research of the last two decades regarding the influence of stress on the developing brain. Both, animal and human studies will shed light on the effect of pre- and postnatal stress demonstrating an influence of early life stressors reaching far into adulthood. A direct influence of stress on multiple developmental characteristics has been postulated and shown. The results of this review will underline the necessity of early life programs focusing stress reduction and resilience in children and their parents. Also, a need for programs targeting stress reduction in pregnancy will be demonstrated and emphasized.


Assuntos
Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Adaptação Psicológica , Adulto , Animais , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Criança , Feminino , Humanos , Pais/psicologia , Gravidez , Estresse Psicológico/prevenção & controle
6.
Pan Afr Med J ; 33: 188, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31692728

RESUMO

Brain radionecrosis is a rare but life-threatening complication of external-beam radiotherapy for ENT cancers, in particular of the nasopharynx, and for brain tumors. Very few studies were conducted on this complication in the African population as well as in the Maghreb population. Therefore our study aims to describe the demographic, clinical, paraclinical, therapeutic and evolutionary features of cerebral radionecrosis in the Department of Neurology at the Mohammed V Military Teaching Hospital in Rabat over a period of 18 years (2000-2017). The study involved 4 women and 13 men, with an average age of 50 years. The mean time between the end of the radiotherapy and the onset of neurological signs was 28 months. Systematic Brain MRI, sometimes complemented by spectro-MRI, allowed the diagnosis in 100% of cases. Etiologically, this complication occurred after radiotherapy for nasopharyngeal carcinoma and cancer of the larynx in all cases. Fifteen patients were treated with a combination of: bolus application of corticosteroids, platelet aggregation inhibitors associated with hyperbaric oxygen therapy with good evolution of two patients in whom oxygen therapy was contraindicated due to a lung problem and ENT cancer, received a combination of bolus application of corticosteroids and platelet aggregation inhibitors with unchanged evolution. These results demonstrate the importance of early diagnosis in patients with potentially serious conditions, in particular neuropsychiatric conditions, as well as of treatment combining bolus application of corticosteroids and hyperbaric oxygen therapy because this is the best guarantee of a favorable outcome, without omitting the crucial role of preventive measures.


Assuntos
Encéfalo/patologia , Oxigenação Hiperbárica/métodos , Lesões por Radiação/diagnóstico por imagem , Corticosteroides/administração & dosagem , Adulto , Idoso , Feminino , Hospitais Militares , Humanos , Neoplasias Laríngeas/radioterapia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Marrocos , Neoplasias Nasofaríngeas/radioterapia , Necrose , Inibidores da Agregação de Plaquetas/administração & dosagem , Lesões por Radiação/terapia , Estudos Retrospectivos
7.
Medicine (Baltimore) ; 98(44): e17797, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689857

RESUMO

RATIONALE: Acute necrotizing encephalopathy (ANE) is a rapidly progressing disease associated with frequent neurologic sequelae and has poor prognosis. Currently, the diagnosis and treatment of ANE rely on neuroradiologic findings and offering supportive care. Here, we report the successful treatment of a teenager diagnosed with ANE using combination of high-dose methylprednisolone and oseltamivir. PATIENT CONCERNS: The patient, a 15-year-old female, presented with impaired consciousness and seizures secondary to acute upper respiratory tract infection. A series of brain magnetic resonance images (MRIs) were obtained toward establishing a possible diagnosis. DIAGNOSIS: Based on the history of presenting illness and subsequent brain MRI scans, the patient was diagnosed to be suffering from ANE. INTERVENTIONS: Following the diagnosis, the patient was placed on therapy comprising of high-dose methylprednisolone and oseltamivir. OUTCOMES: After treatment with methylprednisolone and oseltamivir for 15 days, the patient recovered nearly completely from ANE as confirmed by subsequent brain MRI scans. No complications or other emerging clinical symptoms were noted for the duration of follow-up that lasted 6 months. LESSONS: Contrary to common reports, ANE can occur beyond pediatric populations and its treatment should not be restricted to supportive care. Our case suggests that the use of high-dose corticosteroids and oseltamivir leads to promising prognosis.


Assuntos
Encéfalo/diagnóstico por imagem , Encefalite Viral/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Infecções Respiratórias/complicações , Convulsões/diagnóstico por imagem , Adolescente , Corticosteroides/uso terapêutico , Antivirais/uso terapêutico , Encéfalo/patologia , Encéfalo/virologia , China , Encefalite Viral/tratamento farmacológico , Encefalite Viral/virologia , Feminino , Humanos , Necrose/diagnóstico por imagem , Necrose/virologia , Oseltamivir/uso terapêutico , Prognóstico , Infecções Respiratórias/virologia , Convulsões/patologia , Convulsões/virologia
9.
Life Sci ; 237: 116929, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610210

RESUMO

LncRNA small nucleolar RNA host gene 3 (Snhg3) has been involved in cell proliferation and migration in malignant cells. However, its role in regulating functions of non-malignant cells has been hardly reported. Here, we found Snhg3 expression was sharply induced in primary brain microvascular endothelial cells (BMVECs) treated with oxygen-and-glucose-deprivation (OGD) plus hemin, an in vitro model of intracerebral hemorrhage (ICH). Downregulation of Snhg3 by siRNA transfection improved cell proliferation and migration abilities and reduced cell apoptosis and monolayer permeability in BMVECs under treatment with OGD plus hemin. Snhg3 overexpression suppressed cell proliferation and migration and increased cell apoptosis and monolayer permeability under normal condition. In ICH rats, downregulation of Snhg3 by siRNA injection improved behavioral and histological manifestations, including number of right turns, limb placement score, integrity of blood-brain barrier (BBB), brain water content and cell apoptosis in vivo. In the mechanism exploration, we found that, TWEAK and Snhg3 displayed a positive correlation with each other. Snhg3 overexpression increased expression of TWEAK protein and its receptor Fn14, that were also induced by OGD plus hemin, activating the downstream neuroinflammatory pathway STAT3 and enhancing the secretion of MMP-2/9. Finally, the TWEAK-siRNA, the Fn14 inhibitor ATA and the STAT3 blocker AG490 were respectively used to treat BMVECs under treatment with OGD plus hemin. Our results showed either TWEAK downregulation, Fn14 inhibition, or STAT3 blockade, could rescue Snhg3-induced impairment of BMVEC functions. In conclusion, the lncRNA Snhg3 contributes to dysfunction of cerebral microvascular cells in ICH rats by activating the TWEAK/Fn14/STAT3 pathway.


Assuntos
Encéfalo/patologia , Hemorragia Cerebral/patologia , Citocina TWEAK/metabolismo , Endotélio Vascular/patologia , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/metabolismo , Receptor de TWEAK/metabolismo , Animais , Comportamento Animal , Encéfalo/metabolismo , Células Cultivadas , Hemorragia Cerebral/genética , Hemorragia Cerebral/metabolismo , Circulação Cerebrovascular/fisiologia , Citocina TWEAK/genética , Endotélio Vascular/metabolismo , Regulação da Expressão Gênica , Masculino , Microvasos/metabolismo , Microvasos/patologia , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/genética , Receptor de TWEAK/genética , Cicatrização
10.
Radiol Clin North Am ; 57(6): 1199-1216, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582045

RESUMO

Radiographic monitoring of posttreatment glioblastoma is important for clinical trials and determining next steps in management. Evaluation for tumor progression is confounded by the presence of treatment-related radiographic changes, making a definitive determination less straight-forward. The purpose of this article was to describe imaging tools available for assessing treatment response in glioblastoma, as well as to highlight the definitions, pathophysiology, and imaging features typical of true progression, pseudoprogression, pseudoresponse, and radiation necrosis.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Diagnóstico por Imagem/métodos , Glioblastoma/diagnóstico por imagem , Glioblastoma/radioterapia , Lesões por Radiação/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Progressão da Doença , Glioblastoma/patologia , Humanos , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Imagem Multimodal , Necrose , Tomografia por Emissão de Pósitrons , Lesões por Radiação/patologia
11.
Cancer Invest ; 37(9): 501-505, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583922

RESUMO

Leptomeningeal metastasis (LM) in solid tumors are rare, even more in renal cell carcinoma (RCC). To date there is a lack of consensual treatment modalities of leptomeningeal metastasis. Furthermore, with the improvement of outcomes and more effective systemic targeted therapies, the management of leptomeningeal metastasis becomes a real challenge. We here report two cases of RCC with leptomeningeal metastasis at initial diagnosis. Both patients had concurrent adjacent skull bone metastasis. Therapeutic management of both patients consisted in surgical resection, followed by radiotherapy in one case. Systemic treatment was delayed according to current recommendations for the management of metastatic RCC. The aim of this work is to report the therapeutic approach and related outcomes and also provide a review of the currently available literature on leptomeningeal disease in renal cell carcinoma. Indeed, local treatment with curative outcome of meningeal location in RCC should be performed specially in LM at initial diagnosis.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Neoplasias Meníngeas/secundário , Neoplasias Cranianas/secundário , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/radioterapia , Terapia Combinada , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirurgia , Pessoa de Meia-Idade , Neoplasias Cranianas/radioterapia , Neoplasias Cranianas/cirurgia , Sunitinibe/uso terapêutico , Resultado do Tratamento
12.
Artigo em Russo | MEDLINE | ID: mdl-31577268

RESUMO

The possibility of segmenting three-dimensional objects by DICOM-series is well known and available both on specialized workstations and on personal computers. The technique, however, is relatively rarely used in clinical practice, and we believe that the benefits of preoperative preparation using segmented 3D models are underestimated. The article is devoted to our experience in using segmentation of anatomical structures based on CT and MRI for preoperative preparation for surgical operations performed in neurosurgical departments on patients with vascular pathology. The paper discusses the types and possibilities of segmentation, provides some examples describing the clinical use of the technique.


Assuntos
Encéfalo , Modelos Anatômicos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Imagem por Ressonância Magnética
13.
Artigo em Russo | MEDLINE | ID: mdl-31577269

RESUMO

OBJECTIVE: The aim of this study was to estimate the prognostic value of magnetic resonance imaging (MRI) classification of traumatic brain lesion localization and levels in patients with a brain injury of various severity in a few days to three weeks after the injury. MATERIAL AND METHODS: The cohort of 278 patients with traumatic brain injury (TBI) of various severity aged 8-74 y.o. (average -31.4±13.8, median - 29 (21.3; 37.0) was included in the analysis. The severity of TBI at admission varied from 3 to 15 Glasgow coma scores (GCS) (average - 8±4, median - 7 (5; 12). The main indications and conditions for MRI were: inconsistency between computed tomography (CT) data and neurological status, the necessity to clarify the location and type of brain damage, the absence of metal implants, the stabilization of the patient's vital functions, etc. MRI was performed during the first three weeks after the injury using T1, T2, T2-FLAIR, DWI, T2*GRE, SWAN sequences. The damage to the brain was classified according to 8 grades depending on the lesion levels (cortical-subcortical level, corpus callosum, basal ganglia and/or thalamus, and/or internal, and/or external capsules, uni- or bilateral brain stem injury at a different level). Outcomes were assessed by the Glasgow outcome scale (GOS) 6 months after injury. RESULTS: The significant correlations were found for the entire cohort between MRI grading and TBI severity (by GCS) and outcome (by GOS) of the injury (R=-0.66; p<0.0001; R=-0.69; p<0.0001, respectively). A high accuracy (77%), sensitivity (77%) and specificity (76%) of the proposed MRI classification in predicting injury outcomes (AUC=0.85) were confirmed using the logistic regression and ROC analysis. The assessment of MRI-classification prognostic value in subgroups of patients examined during the first, second, and third weeks after injury showed significant correlations between the GCS and the GOS as well as between MRI-grading and GCS, and GOS in all three subgroups. In the subgroup of patients examined during the first 14 days after the injury, the correlation coefficients were higher compared with those obtained in a subgroup examined 15-21 days after the injury. The highest correlations between MRI grading, TBI severity, and the outcome were found in the subgroup of patients who underwent MRI in the first three days after the injury (n=58). CONCLUSION: The proposed MRI classification of traumatic brain lesion levels and localization based on the use of different MR sequences reliably correlated with the clinical estimate of TBI severity by GCS and the outcomes by GOS in patients examined during the first three weeks after injury. The strongest correlation was observed for patients examined during the first three days after the injury.


Assuntos
Lesões Encefálicas , Imagem por Ressonância Magnética , Neuroimagem , Adolescente , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Lesões Encefálicas/diagnóstico por imagem , Criança , Escala de Coma de Glasgow , Escala de Resultado de Glasgow , Humanos , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
15.
J Biol Regul Homeost Agents ; 33(5): 1359-1367, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31659887

RESUMO

To study the expression changes of inflammatory factors heme oxygenase-1 (HO-1), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) in intracerebral hemorrhage (ICH), brain tissues surrounding hematoma were collected from ICH patients. The expressions of HO-1, TNF-α, IL- 1ß, and other genes were examined at different time points of ICH. Changes in HO-1, TNF-α, and IL-1ß positive cell numbers after ICH were detected by immunohistochemical staining. The results showed that the expressions of HO-1, TNF-α, and IL-1ß had no significant changes in brain tissues surrounding hematoma within 6 hours after ICH (P > 0.05). Their expressions during 6-24 hours and 24-72 hours after ICH increased constantly. After reaching the peak, they remained steady or slightly decreased after 72 hours. The dynamic expression changes of HO-1, TNF-α, and IL-1ß were observed and their development trends were interfered timely to alleviate the secondary neurological impairment after ICH, which was significant to prevent ICH.


Assuntos
Encéfalo/metabolismo , Hemorragia Cerebral/patologia , Hematoma/metabolismo , Heme Oxigenase-1/metabolismo , Interleucina-1beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Encéfalo/patologia , Hematoma/patologia , Humanos
16.
Sheng Li Xue Bao ; 71(5): 705-716, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31646324

RESUMO

The aim of the present study was to investigate the differences of the pathological changes and cognitive function after bilateral common carotid artery occlusion (BCCAO) between Sprague-Dawley (SD) and Wistar rats. Male SD and Wistar rats were randomly divided into 2 groups, respectively: sham operated (S-sham and W-sham) and operated (S-BCCAO and W-BCCAO) groups. The survival rate and the rate of loss of pupillary light reflex (PLR) were observed on day 1, 3, 7, 14 and 28 after the operation, and the light-dark box, Y-maze and odor recognition tests were performed to detect cognitive function on day 28 after the operation. HE and Luxol fast blue staining were used to observe the pathological changes of gray matter (hippocampus), white matter (optical tract), optic nerve, and retina. The results showed that the survival rate of the W-BCCAO group was 62.5%, and PLR loss rate was 100%; whereas the survival rate of the S-BCCAO group was 100%, and PLR loss rate was 58.3%. In the W-BCCAO group, percentages of time spent and distance traveled in the light box were more than those in the W-sham group, but there was no statistical significance between the S-BCCAO and S-sham groups. In the S-BCCAO group, the percentages of time spent and distance traveled in the III arm (labyrinth arm) of the Y-maze were less than those in the S-sham group, but no statistical significance was found between the W-BCCAO group and W-sham group. In the S-BCCAO group, the discrimination ratio of the odor recognition task was less than that in the S-sham group, but no statistical significance could be seen between the W-BCCAO and W-sham groups. Ischemic injury was observed in the CA1 area of the hippocampus in the S-BCCAO group, but no readily visible damage was observed in the W-BCCAO group. Ischemic injury of the visual beam and optic nerve was observed in both the S-BCCAO and W-BCCAO groups. Compared with the corresponding sham groups, the S-BCCAO and W-BCCAO groups showed serious retinal damage with significant thinner retina. The ganglion cell layer (GCL), inner plexiform layer (IPL), and outer plexiform layer (OPL) were thinner in the S-BCCAO group, but no statistical significances were shown in the other layers. All the layers, except the outer nuclear layer (ONL), were significantly thinner in the W-BCCAO group. The results indicate that there are differences of the pathological changes in the hippocampus and visual conduction pathway after BCCAO between SD and Wistar rats, and the degree of learning and memory injury was also different, which suggests that the vascular dementia model of different rat strains should be selected according to research purpose.


Assuntos
Encéfalo/patologia , Doenças das Artérias Carótidas/patologia , Artéria Carótida Primitiva/patologia , Cognição , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Ratos Wistar
17.
J Cancer Res Clin Oncol ; 145(12): 3099-3104, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549227

RESUMO

BACKGROUND: The American Society of Clinical Oncology and Friends of Cancer Research submitted recommendations to the FDA to reduce barriers in clinical trial participation. They proposed the removal of several specific exclusion criteria, including brain metastasis. Clinical trials involving small cell lung cancer (SCLC) have varying exclusion criteria regarding brain metastasis. METHODS: We completed an online search of clinicaltrials.gov for the query "SCLC, extensive stage." The trials were classified into a group of strict exclusion, allowed only if treated, allowed without treatment, or undefined. Relationships between status of brain metastasis in exclusion criteria and study characteristics (trial status, trial design, sponsor, location, and treatment groups) were investigated by Chi-squared test. The trends of exclusion status were investigated by a comparison against the variable time. RESULTS: Of the 204 eligible trials, 32 strictly excluded any form or history of CNS metastases, 129 allowed patients that are undergoing or have undergone CNS-specific therapy, 9 allowed patients without any CNS-specific therapy, and 34 did not mention any criteria involving CNS metastases. Studies conducted outside the United States and with single systemic therapy were associated with strict exclusion of brain metastasis (p = 0.026 and 0.039, respectively). The proportion of clinical trials with strict exclusion has remained around 15% for the past few decades. CONCLUSION: Non-US and single systemic therapy studies are more commonly associated with strict exclusion of brain metastasis in ES-SCLC trials. The strict exclusion of brain metastases in clinical trials has remained relatively constant for the past few decades.


Assuntos
Neoplasias Encefálicas/patologia , Encéfalo/patologia , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Animais , Neoplasias Encefálicas/secundário , Ensaios Clínicos como Assunto , Humanos , Estados Unidos
18.
Nat Neurosci ; 22(10): 1624-1634, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31551593

RESUMO

Hundreds of genes are implicated in autism spectrum disorder (ASD), but the mechanisms through which they contribute to ASD pathophysiology remain elusive. Here we analyzed leukocyte transcriptomics from 1- to 4-year-old male toddlers with ASD or typical development from the general population. We discovered a perturbed gene network that includes highly expressed genes during fetal brain development. This network is dysregulated in human induced pluripotent stem cell-derived neuron models of ASD. High-confidence ASD risk genes emerge as upstream regulators of the network, and many risk genes may impact the network by modulating RAS-ERK, PI3K-AKT and WNT-ß-catenin signaling pathways. We found that the degree of dysregulation in this network correlated with the severity of ASD symptoms in the toddlers. These results demonstrate how the heterogeneous genetics of ASD may dysregulate a core network to influence brain development at prenatal and very early postnatal ages and, thereby, the severity of later ASD symptoms.


Assuntos
Transtorno do Espectro Autista/genética , Redes Reguladoras de Genes/genética , Transtorno do Espectro Autista/patologia , Encéfalo/embriologia , Encéfalo/patologia , Pré-Escolar , Desenvolvimento Fetal/genética , Humanos , Lactente , Leucócitos , Sistema de Sinalização das MAP Quinases/genética , Masculino , Mutação/genética , Células-Tronco Neurais , Proteína Oncogênica v-akt/genética , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais/genética , Via de Sinalização Wnt/genética , beta Catenina/genética
20.
Adv Exp Med Biol ; 1161: 125-131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562627

RESUMO

Ischemic strokes are caused by one or more blood clots that typically obstruct one of the major arteries in the brain, but frequently also result in leakage of the blood-brain barrier and subsequent hemorrhage. While it has long been known that the enzyme 12/15-lipoxygenase (12/15-LOX) is up-regulated following ischemic strokes and contributes to neuronal cell death, recent research has shown an additional major role for 12/15-LOX in causing this hemorrhagic transformation. These findings have important implications for the use of 12/15-LOX inhibitors in the treatment of stroke.


Assuntos
Araquidonato 15-Lipoxigenase , Isquemia Encefálica , Hemorragia , Acidente Vascular Cerebral , Barreira Hematoencefálica/patologia , Encéfalo/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/fisiopatologia , Hemorragia/etiologia , Hemorragia/fisiopatologia , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia
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