RESUMEN
Brain imaging using conventional head coils presents several problems in routine magnetic resonance (MR) examination, such as anxiety and claustrophobic reactions during scanning with a head coil, photon attenuation caused by the MRI head coil in positron emission tomography (PET)/MRI, and coil constraints in intraoperative MRI or MRI-guided radiotherapy. In this paper, we propose a super resolution generative adversarial (SRGAN-VGG) network-based approach to enhance low-quality brain images scanned with body coils. Two types of T1 fluid-attenuated inversion recovery (FLAIR) images scanned with different coils were obtained in this study: joint images of the head-neck coil and digital surround technology body coil (H+B images) and body coil images (B images). The deep learning (DL) model was trained using images acquired from 36 subjects and tested in 4 subjects. Both quantitative and qualitative image quality assessment methods were performed during evaluation. Wilcoxon signed-rank tests were used for statistical analysis. Quantitative image quality assessment showed an improved structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR) in gray matter and cerebrospinal fluid (CSF) tissues for DL images compared with B images (P <.01), while the mean square error (MSE) was significantly decreased (P <.05). The analysis also showed that the natural image quality evaluator (NIQE) and blind image quality index (BIQI) were significantly lower for DL images than for B images (P <.0001). Qualitative scoring results indicated that DL images showed an improved SNR, image contrast and sharpness (P<.0001). The outcomes of this study preliminarily indicate that body coils can be used in brain imaging, making it possible to expand the application of MR-based brain imaging.
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Encéfalo , Procesamiento de Imagen Asistido por Computador , Encéfalo/diagnóstico por imagen , Estudios de Factibilidad , Humanos , Redes Neurales de la Computación , Neuroimagen , TecnologíaRESUMEN
A thorough understanding of inner ear anatomy is important for investigators. However, investigation of the mouse inner ear is difficult due to the limitations of imaging techniques. X-ray phase contrast tomography increases contrast 100-1,000 times compared with conventional X-ray imaging. This study aimed to investigate inner ear anatomy in a fresh post-mortem mouse using X-ray phase contrast tomography and to provide a comprehensive atlas of microstructures with less tissue deformation. All experiments were performed in accordance with our institution's guidelines on the care and use of laboratory animals. A fresh mouse cadaver was scanned immediately after sacrifice using an inline phase contrast tomography system. Slice images were reconstructed using a filtered back-projection (FBP) algorithm. Standardized axial and coronal planes were adjusted with a multi-planar reconstruction method. Some three-dimensional (3D) objects were reconstructed by surface rendering. The characteristic features of microstructures, including otoconia masses of the saccular and utricular maculae, superior and inferior macula cribrosae, single canal, modiolus, and osseous spiral lamina, were described in detail. Spatial positions and relationships of the vestibular structures were exhibited in 3D views. This study investigated mouse inner ear anatomy and provided a standardized presentation of microstructures. In particular, otoconia masses were visualized in their natural status without contrast for the first time. The comprehensive anatomy atlas presented in this study provides an excellent reference for morphology studies of the inner ear.
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Oído Interno/anatomía & histología , Microscopía de Contraste de Fase , Tomografía Computarizada por Rayos X , Animales , Oído Interno/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional/instrumentación , Imagenología Tridimensional/métodos , Ratones , Membrana Otolítica/anatomía & histología , Membrana Otolítica/diagnóstico por imagenRESUMEN
BACKGROUND: Cerebral sparganosis is the most serious complication of human sparganosis. Currently, there is no standard for the treatment of inoperable patients. Conventional-dose praziquantel therapy is the most reported treatment. However, the therapeutic outcomes are not very effective. High-dose praziquantel therapy is a useful therapeutic choice for many parasitic diseases that is well tolerated by patients, but it has not been sufficiently evaluated for cerebral sparganosis. This study aims to observe the prognoses following high-dose praziquantel therapy in inoperable patients and the roles of MRI and peripheral eosinophil absolute counts during follow-up. METHODOLOGY: Baseline and follow-up epidemiological, clinical, radiological and therapeutic data related to 10 inoperable patients with cerebral sparganosis that were treated with repeated courses of high-dose praziquantel therapy, with each course consisting of 25 mg/kg thrice daily for 10 days were assessed, followed by analyses of the prognoses, MRI findings and peripheral eosinophil absolute counts. PRINCIPAL FINDINGS: Baseline clinical data: the clinical symptoms recorded included seizures, hemiparesis, headache, vomiting and altered mental status. Peripheral blood eosinophilia was found in 3 patients. The baseline radiological findings were as follows. Motile lesions were observed in 10 patients, including aggregated ring-like enhancements, tunnel signs, serpiginous and irregular enhancements. Nine of the 10 patients had varying degrees of white matter degeneration, cortical atrophy and ipsilateral ventricle dilation. The follow-up clinical data were as follows. Clinical symptom relief was found in 8 patients, symptoms were eliminated in 1 patient, and symptoms showed no change from baseline in 1 patient. Peripheral blood eosinophilia was found in 2 patients. The follow-up radiological findings were as follows. Motile lesions that were transformed into stable, chronic lesions were found in 8 patients, and motile lesions that were eliminated completely were found in 2 patients. CONCLUSIONS: High-dose praziquantel therapy for cerebral sparganosis is effective. The radiological outcomes of motile lesions are an important indicator during the treatment process, especially during follow-ups after clinical symptoms have improved. Peripheral eosinophil absolute counts cannot be used as an effective prognostic indicator.
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Antihelmínticos/uso terapéutico , Praziquantel/uso terapéutico , Esparganosis/tratamiento farmacológico , Plerocercoide/efectos de los fármacos , Adolescente , Adulto , Animales , Antihelmínticos/administración & dosificación , Anticuerpos Antihelmínticos/sangre , Niño , Epilepsia/tratamiento farmacológico , Epilepsia/parasitología , Femenino , Estudios de Seguimiento , Enfermedades Transmitidas por los Alimentos/parasitología , Humanos , Masculino , Persona de Mediana Edad , Oxcarbazepina/uso terapéutico , Praziquantel/administración & dosificación , Estudios Retrospectivos , Plerocercoide/aislamiento & purificación , Resultado del Tratamiento , Adulto JovenRESUMEN
The retina is one of the most tiny and sophisticated tissues of the body. Three dimensional (3D) visualization of the whole retina is valuable both in clinical and research arenas. The tissue has been predominantly assessed by time-consuming histopathology and optical coherence tomography (OCT) in research and clinical arenas. However, none of the two methods can provide 3D imaging of the retina. The purpose of this study is to give a volumetric visualization of rat retina at submicron resolution, using an emerging imaging technique-phase-contrast X-ray CT. A Sprague-Dawley (SD) rat eye specimen was scanned with X-ray differential phase contrast tomographic microscopy (DPC-microCT) equipped at the Swiss Light Source synchrotron. After scanning, the specimen was subjected to routine histology procedures and severed as a reference. The morphological characteristics and signal features of the retina in the DPC-microCT images were evaluated. The total retina and its sublayers thicknesses were measured on the DPC-microCT images and compared with those obtained from the histological sections. The retina structures revealed by DPC-microCT were highly consistent with the histological section. In this study, we achieved nondestructive 3D visualization of SD rat retina. In addition to detailed anatomical structures, the objective parameters provided by DPC-microCT make it a useful tool for retinal research and disease diagnosis in the early stage.
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Imagenología Tridimensional/métodos , Retina/anatomía & histología , Retina/ultraestructura , Tomografía de Coherencia Óptica/métodos , Animales , Medios de Contraste , Microscopía de Contraste de Fase/métodos , Prueba de Estudio Conceptual , Ratas , Ratas Sprague-DawleyRESUMEN
Chlorotoxin (CTX) is a 36-amino acid peptide derived from Leiurus quinquestriatus (scorpion) venom, which inhibits low-conductance chloride channels in colonic epithelial cells. It has been reported that CTX also binds to matrix metalloproteinase-2 (MMP-2), membrane type-1 MMP, and tissue inhibitor of metalloproteinase-2, as well as CLC-3 chloride ion channels and other proteins. Pancreatic cancer cells require the activation of MMP-2 during invasion and migration. In this study, the fusion protein was generated by joining the CTX peptide to the amino terminus of the human IgG-Fc domain without a hinge domain, the monomeric form of chlorotoxin (M-CTX-Fc). The resulting fusion protein was then used to target pancreatic cancer cells (PANC-1) in vitro. M-CTX-Fc decreased MMP-2 release into the media of PANC-1 cells in a dose-dependent manner. M-CTX-Fc internalization into PANC-1 cells was observed. When the cells were treated with chlorpromazine (CPZ), the internalization of the fusion protein was reduced, implicating a clathrin-dependent internalization mechanism of M-CTX-Fc in PANC-1 cells. Furthermore, M-CTX-Fc clearly exhibited the inhibition of the migration depending on the concentration, but human IgG, as negative control of Fc, was not affected. The M-CTX-Fc may be an effective instrument for targeting pancreatic cancer.
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Inmunoglobulina G/genética , Metaloproteinasa 2 de la Matriz/biosíntesis , Neoplasias Pancreáticas/tratamiento farmacológico , Venenos de Escorpión/administración & dosificación , Línea Celular Tumoral , Canales de Cloruro/biosíntesis , Canales de Cloruro/genética , Regulación Neoplásica de la Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Fragmentos Fc de Inmunoglobulinas/genética , Fragmentos Fc de Inmunoglobulinas/inmunología , Inmunoglobulina G/inmunología , Metaloproteinasa 2 de la Matriz/efectos de los fármacos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Venenos de Escorpión/químicaRESUMEN
OBJECTIVES: To evaluate the role of contrast-enhanced transrectal ultrasonography (CE-TRUS) for detecting prostate carcinoma. METHODS: Sixty-five patients with elevated serum prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE) were assessed using transrectal ultrasound (TRUS) and CE-TRUS. In all the patients, CE-TRUS was performed with intravenous injection of contrast agent (SonoVue, 2.4 ml) before biopsy. The cancer detection rates of the two techniques were compared. False-positive and false-negative findings related to CE-TRUS were analyzed in comparison to the pathological results of biopsy or radical prostatectomy. The targeted biopsy to abnormal CE-TRUS areas was also compared to systematic biopsy. RESULTS: Prostate cancer was detected in 29 of the 65 patients. CE-TRUS showed rapid focal enhancement or asymmetric vessels of peripheral zones in 28 patients; 23 of them had prostate cancer. CE-TRUS had 79.3% sensitivity, compared to 65.5% of TRUS (P<0.05). There were five false-positive and six false-negative findings from CE-TRUS. Benign prostate hyperplasia, and acute and chronic prostatitis were important causes related to the false-positive results of CE-TRUS. Prostate cancer originating from the transition zone or peripheral zone with lower PSA levels, small-size foci, and moderately or well-differentiated tumor was missed by CE-TRUS. The cancer detection rate of targeted biopsy (75%, 33/44 cores) was significantly higher than one of systematic biopsy (48.2%, 162/336) in those 28 cases (P<0.05). In addition, no significant correlation was found between the cancer detection rate with CE-TRUS and serum PSA levels. CONCLUSION: CE-TRUS may improve the detection rate of prostate cancer through targeted biopsy of contrast-enhanced abnormalities. Our findings indicate that systematic biopsies should not be eliminated on the basis of false-positive and false-negative findings related to CE-TRUS.
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Fosfolípidos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/epidemiología , Hexafluoruro de Azufre , Ultrasonografía/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , China/epidemiología , Medios de Contraste , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Recto , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
The p38 mitogen-activated protein kinase (MAPK) plays an important role in apoptosis and is also involved in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). Here, we sought to examine whether inhibition of p38 MAPK could attenuate cerebral vasospasm and investigate the underlying mechanisms in a rabbit SAH model. SAH was established in rabbits (n=12/group) using the double-hemorrhage method. We observed apparent vasospasm in the basilar arteries of rabbits with SAH, which was significantly attenuated by SB203580, a selective p38MAPK inhibitor. Immunoblotting assays showed enhanced phosphorylation of p38 MAPK and ATF2 and increased caspase-3 cleavage following SAH, which were, however, markedly suppressed by SB203580. TUNEL staining further revealed significant apoptosis in the basilar arteries of rabbits with SAH, which was scantly present in rabbits treated with SB203580. Our results demonstrated that p38 MAPK was activated in cerebral vasospasm and associated with increased apoptosis in the basilar arteries and p38 MAPK inhibition suppressed apoptosis, suggesting that p38 MAPK could be a novel therapeutic target for cerebral vasospasm.
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Inhibidores Enzimáticos/farmacología , Imidazoles/farmacología , Piridinas/farmacología , Hemorragia Subaracnoidea/tratamiento farmacológico , Vasoespasmo Intracraneal/tratamiento farmacológico , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Factor de Transcripción Activador 2/metabolismo , Animales , Apoptosis/efectos de los fármacos , Arteria Basilar/efectos de los fármacos , Arteria Basilar/patología , Arteria Basilar/fisiopatología , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Inyecciones Intraventriculares , Fosforilación , Conejos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/enzimología , Vasoespasmo Intracraneal/complicaciones , Vasoespasmo Intracraneal/enzimología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
The pathogenesis of cerebral vasospasm is closely associated with inflammation and immune response in arterial walls. Recently, the authors proved the key role of Toll-like receptor (TLR)4 in the development of vasospasm in experimental subarachnoid hemorrhage (SAH) model. Because peroxisome proliferator-activated receptor (PPAR) gamma agonists are identified as effective inhibitors of TLR4 activation, we investigated the anti-inflammation properties of PPAR-gamma agonist rosiglitazone in basilar arteries in a rat experimental SAH model and evaluated the effects of rosiglitazone on vasospasm. Inflammatory responses in basilar arteries were assessed by immunohistochemical staining for intercellular molecule (ICAM)-1 and myeloperoxidase (MPO). Expression of TLR4 was determined by western blot analysis. The degree of cerebral vasospasm was evaluated by measuring the mean diameter and cross-sectional area of basilar arteries. Rosiglitazone suppressed the SAH-induced inflammatory responses in basilar arteries by inhibiting the TLR4 signalling. Furthermore, rosiglitazone could attenuate cerebral vasospasm following SAH. Therefore, we suggested that PPAR-gamma agonists may be potential therapeutic agents for cerebral vasospasm.
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PPAR gamma/agonistas , PPAR gamma/fisiología , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/metabolismo , Tiazolidinedionas/uso terapéutico , Vasodilatadores/uso terapéutico , Vasoespasmo Intracraneal/tratamiento farmacológico , Vasoespasmo Intracraneal/metabolismo , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Sprague-Dawley , Rosiglitazona , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Hemorragia Subaracnoidea/patología , Receptor Toll-Like 4/antagonistas & inhibidores , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/fisiología , Vasoespasmo Intracraneal/etiologíaRESUMEN
OBJECTIVE: To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) as a key transcription factor of cytoprotection against inflammation in the spinal cord upregulation of matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α(TNF-α) after spinal cord injury (SCI). METHODS: Wild-type Nrf2(+/+) and Nrf2(-/-)-deficient mice were subjected to a murine SCI model induced by the application of vascular clips (force of 10 g) to the dura after a three-level T8-T10 laminectomy. The wet/dry weight ratio was used to reflect the percentage of water content of impaired spinal cord tissue at 48 h after SCI. The mRNA levels of MMP-9 were determined using reverse-transcriptase polymerase chain reaction (RT-PCR), and the protein levels of TNF-α and MMP-9 were detected by enzyme-linked immunosorbent assay at 24 h after SCI. Furthermore, gelatin zymography analysis was used to show MMP-9 activity of spinal cord tissue at 24 h after SCI. Software SPSS 16.0 was used for the statistical analysis. RESULTS: After SCI, spinal cord water content, the expression of TNF-α and MMP-9 all increased in both injured Nrf2(+/+) and Nrf2(-/-) mice compared with their respective sham-operated mice. However, Nrf2(-/-) mice were shown to have more severe spinal cord edema, more TNF-α expression, more production and activity of MMP-9 compared with their wild-type Nrf2(+/+) counterparts after SCI (P < 0.05). CONCLUSIONS: The results suggest that Nrf2 plays an important protective role in limiting the spinal cord upregulation of TNF-α and MMP-9 after SCI. It may be a new therapeutic target of SCI.
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Metaloproteinasa 9 de la Matriz/metabolismo , Factor 2 Relacionado con NF-E2/genética , Traumatismos de la Médula Espinal/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Genotipo , Masculino , Ratones , Ratones Endogámicos ICR , Ratones Noqueados , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/genéticaRESUMEN
Inflammation plays an important role in the pathogenesis of secondary damage after spinal cord injury (SCI). The present study explored the effect of sulforaphane (SFN), a potent anti-inflammatory extract of cruciferous vegetables, on the expression of two inflammatory mediators, metalloproteinase (MMP)-9 and TNF-α, in a murine model of SCI. Murine spinal cord injury was induced by the application of vascular clips (force of 10 g) to the dura after a three-level T8-T10 laminectomy. The wet/dry weight ratio was used to reflect the percentage of water content of impaired spinal cord tissue at 48 hr after SCI. The mRNA levels of MMP-9 were determined using the reverse-transcriptase polymerase chain reaction (RT-PCR), and protein levels of TNF-α and MMP-9 were detected by enzyme-linked immunosorbent assays (ELISA) at 24 hr after SCI. Gelatin zymography was used to determine MMP-9 activity of spinal cord tissue at 24 hr after SCI. Mice treated with SFN at 1 hr after SCI had lower expression and activity of MMP-9 compared to mice with SCI. The decrease of MMP-9 in mice treated with SFN was associated with decreased levels of spinal cord water content and TNF-α. In summary, suforaphane decreases MMP-9 and TNF-α expression and vascular permeability changes following spinal cord injury in mice.
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Metaloproteinasa 9 de la Matriz/metabolismo , Traumatismos de la Médula Espinal/enzimología , Tiocianatos/farmacología , Animales , Permeabilidad Capilar/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Isotiocianatos , Masculino , Metaloproteinasa 9 de la Matriz/genética , Ratones , Ratones Endogámicos ICR , Tamaño de los Órganos/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Médula Espinal/efectos de los fármacos , Médula Espinal/enzimología , Médula Espinal/patología , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/fisiopatología , Sulfóxidos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Previous studies have demonstrated that mitogen-activated protein kinase (MAPK) is involved in the pathogenesis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Ras, an upstream regulator of MAPK, may be activated following SAH. The aim of this study was to investigate the role of Ras in cerebral vasospasm in a rabbit model of SAH. We first investigated the time course of Ras and ERK1/2 activation in the basilar artery after SAH. Next, for the time point at which Ras was maximally activated, we assessed the effect of FTI-277 (a Ras farnesyltransferase inhibitor) on cerebral vasospasm. SAH was induced by injecting autologous blood into the cisterna magna on both day 0 and day 2. FTI-277 was injected into the cisterna magna every 24 hours, beginning 30 minutes after blood injection to the last day of the experiment. Elevated expression of Ras-GTP and phosphorylated ERK1/2 was detected in the basilar artery after SAH and expression peaked on day 3. FTI-277 administration resulted in lower Ras-GTP and phosphorylated ERK1/2 levels and markedly attenuated vasospasm in the basilar arteries relative to animals that did not receive FTI-277. Our results suggest that Ras protein is activated in the arterial wall after SAH and contributes to vasospasm development.
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Sistema de Señalización de MAP Quinasas/fisiología , Hemorragia Subaracnoidea/metabolismo , Vasoespasmo Intracraneal/metabolismo , Proteínas ras/fisiología , Animales , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/administración & dosificación , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metionina/administración & dosificación , Metionina/análogos & derivados , Metionina/farmacología , Conejos , Distribución Aleatoria , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/enzimología , Vasoespasmo Intracraneal/enzimología , Vasoespasmo Intracraneal/etiología , Proteínas ras/antagonistas & inhibidores , Proteínas ras/biosíntesisRESUMEN
OBJECTIVE: To study the application of DEI technique in imaging the small structures of rabbit eyeball. METHOD: DEI technique was used to image the eyeball of New Zealand white rabbit in vitro. The experiments were performed using beamline 4W1A at the topography station of Beijing Synchrotron Radiation Facility (BSRF). RESULT: DEI image showed clearly the fine structures of the rabbit eyeball, such as the transparent cornea, the sclera, the ciliaris, and the ciliary body. CONCLUSION: DEI is a new X-ray imaging modality which achieves high contrast and spatial resolution. It also showed obvious effect of edge enhancement. DEI has good potential in observing the micro-structures of eyeballs and other small organs.
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Córnea/diagnóstico por imagen , Ojo/diagnóstico por imagen , Difracción de Rayos X/métodos , Animales , Diagnóstico por Imagen/métodos , Conejos , RadiografíaRESUMEN
Inflammation and immune response have been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). Recently, increased TLR4 expression has been associated with the development of cerebral vasospasm in a rabbit model of SAH. Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, effective inhibitors of TLR4 activation, may modulate the vasospasm progression via their anti-inflammation effects. We investigate whether the blood component oxyhemoglobin (OxyHb) can induce the expression of Toll-like receptor (TLR) 4 in vascular smooth muscle cells (VSMCs), and evaluate the modulatory effects of PPARgamma agonist rosiglitazone on OxyHb-induced inflammation in VSMCs. Cultured VSMCs incubated with or without rosiglitazone were exposed to OxyHb at 10muM for up to 48h. Expression of TLR4 was assessed by immunocytochemistry and Western blot analysis. Production of tumor necrosis factor alpha (TNF-alpha) in conditioned medium were quantified by ELISA. A marked increase of TLR4 production and TNF-alpha release was observed at 48h after cells were treated with OxyHb. Rosiglitazone reduced TLR4 immunocytochemistry staining and protein production significantly in VSMCs. A specific antagonist for PPARgamma, GW9662, could reverse the anti-inflammatory effects of rosiglitazone. The results demonstrated that OxyHb exposure could induce TLR4 activation in cultured VSMCs. Rosiglitazone suppressed TLR4 expression and cytokine release via the activation of PPARgamma and may have a therapeutic potential for the treatment of vasospasm following SAH.
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Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Oxihemoglobinas/antagonistas & inhibidores , PPAR gamma/agonistas , Tiazolidinedionas/farmacología , Receptor Toll-Like 4/efectos de los fármacos , Anilidas/farmacología , Animales , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/fisiología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/fisiopatología , Masculino , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Oxihemoglobinas/metabolismo , PPAR gamma/antagonistas & inhibidores , PPAR gamma/metabolismo , Ratas , Ratas Sprague-Dawley , Rosiglitazona , Hemorragia Subaracnoidea/complicaciones , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Vasodilatadores/farmacología , Vasoespasmo Intracraneal/tratamiento farmacológico , Vasoespasmo Intracraneal/metabolismo , Vasoespasmo Intracraneal/fisiopatologíaRESUMEN
Genistein (4',5,7-trihydroxyisoflavone) is the most abundant isoflavone found in the soybean that exhibits an anti-inflammatory effect. The present study was designed to examine the effects of genistein on expression levels of hemolysate-induced proinflammatory and adhesion molecules in SD rat brain microvascular endothelial cells (BMECs). Genistein treatment attenuated hemolysate-induced nuclear factor-kappa B (NF-kappaB) p65 translocation in BMECs. In addition, genistein suppressed the expression levels of tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein 1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1), but not vascular cell adhesion molecule-1 (VCAM-1). The inhibitory rate of 50 pM genistein for TNF-alpha, MCP-1 and ICAM-1 was 65.4%, 60.5% and 54.9% respectively. These inhibitory effects of genistein on proinflammatory and adhesion molecules were not due to decreased BMEC viability as assessed by MTT test. Taken together the present study suggests that genistein suppresses expression levels of hemolysate-induced pro-inflammatory and adhesion molecules in cerebral endothelial cells.
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Moléculas de Adhesión Celular/metabolismo , Extractos Celulares/farmacología , Citocinas/metabolismo , Células Endoteliales/efectos de los fármacos , Endotelio Vascular/citología , Genisteína/farmacología , Fitoestrógenos/farmacología , Animales , Animales Recién Nacidos , Encéfalo/anatomía & histología , Moléculas de Adhesión Celular/clasificación , Moléculas de Adhesión Celular/genética , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citocinas/clasificación , Citocinas/genética , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , FN-kappa B/genética , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
BACKGROUND: The ketogenic diet (the KD) is an effective treatment for intractable epilepsy, especially in the paediatric population, and a growing number of studies have shown the neuroprotective role of the KD. However, few studies focused on the neuroprotective effects of the KD in traumatic brain injury (TBI). The present study aimed to investigate the effects of the KD on TBI. METHODS AND PROCEDURES: Male Sprague-Dawley rats (n = 60) were randomly divided into four groups according to the diet fed (the KD vs normal diet) and whether brain was injured or not. TBI was produced using Feeney weight drop model. Brain oedema was estimated by wet/dry weight ratio; Bax and Bcl-2 mRNA levels were determined by RealTime-PCR; Bax and Bcl-2 protein levels were detected by Western blot. Furthermore, cellular apoptosis in the penumbra area was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) method. MAIN OUTCOMES AND RESULTS: The results indicated that both Bax mRNA and protein levels were significantly elevated 72 hours after TBI and decreased by KD administration. Neither TBI nor the KD affected Bcl-2 mRNA and protein levels. KD administration also reduced brain oedema and cellular apoptosis. CONCLUSION: These results suggest that the KD might be a useful treatment for children suffering from the consequences of TBI.
Asunto(s)
Apoptosis/efectos de los fármacos , Edema Encefálico/metabolismo , Lesiones Encefálicas/dietoterapia , Dieta Cetogénica , Animales , Edema Encefálico/dietoterapia , Edema Encefálico/etiología , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/metabolismo , Modelos Animales de Enfermedad , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that plays an important role in the recruitment of macrophages. Although previous studies have demonstrated that MCP-1 has been shown to be involved in the damaging inflammatory processes associated with stroke, infection, neoplasia, and others in the central nervous system, the role of MCP-1 in the cerebral artery after experimental subarachnoid hemorrhage (SAH) in rats has been largely unexplored. This study was undertaken to investigate the expression of the MCP-1 in SAH model and to clarify the potential role of MCP-1 in cerebral vasospasm. A total of 80 rats were randomly divided into four groups: control group; day 3, day 5, and day 7 groups. Day 3, day 5, and day 7 groups were all SAH groups. The animals in day 3, day 5 and day 7 groups were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2 and were killed on days 3, 5, and 7, respectively. Cross-sectional area of basilar artery was measured and the MCP-1 expression was assessed by real-time PCR, Western blot and immunohistochemistry. The cross-sectional area of basilar artery was found to be 85,373+/-8794 mum(2) in control group, 59,210+/-7281 mum(2) in day 3, 50,536+/-6519 mum(2) in day 5, and 66,360+/-7452 mum(2) in day 7, respectively. The basilar arteries exhibited vasospasm after SAH and became more severe on day 5. The elevated mRNA and protein of MCP-1 were detected after SAH and peaked on day 5. MCP-1 is increasingly expressed in a parallel time course to the development of cerebral vasospasm in a rat experimental model of SAH and these findings might have important implications during the administration of specific MCP-1 antagonists in order to prevent or reduce cerebral vasospasm caused by SAH.
Asunto(s)
Arteria Basilar/fisiología , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Hemorragia Subaracnoidea , Vasoespasmo Intracraneal , Animales , Circulación Cerebrovascular/fisiología , Modelos Animales de Enfermedad , Inmunohistoquímica , Masculino , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Hemorragia Subaracnoidea/inmunología , Hemorragia Subaracnoidea/metabolismo , Hemorragia Subaracnoidea/fisiopatología , Vasoespasmo Intracraneal/inmunología , Vasoespasmo Intracraneal/metabolismo , Vasoespasmo Intracraneal/fisiopatologíaRESUMEN
BACKGROUND: Traumatic brain injury (TBI) can induce an acute intestinal mucosal injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) has a unique role in many physiological stress processes, but its contribution to intestinal mucosal injury after TBI remains to be determined. MATERIALS AND METHODS: Wildtype Nrf2 (+/+) and Nrf2 (-/-) deficient mice were subjected to a moderately severe weight-drop impact head injury. Intestinal mucosal morphological changes, plasma endotoxin, intestinal permeability, apoptosis, inflammatory cytokines, and antioxidant/detoxifying enzymes were measured at 24 hours after TBI. RESULTS: Nrf2 deficient mice were found to be more susceptible to TBI-induced acute intestinal mucosal injury, as characterized by the higher increase in gut structure damage, plasma endotoxin, intestinal permeability, and apoptosis after TBI. This exacerbation of intestinal mucosal injury in Nrf2 deficient mice was associated with increased intestinal mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1beta and interleukin-6, and with decreased intestinal mRNA expression and activity levels of antioxidant and detoxifying enzymes including NAD(P)H: quinone oxidoreductase 1 (NQO1) and glutathione S-transferase alpha-1 (GST-alpha1), compared with their wildtype Nrf2 (+/+) counterparts after TBI. CONCLUSIONS: We show for the first time that mice lacking Nrf2 are more susceptible to TBI-induced acute intestinal mucosal injury. Our data suggests that Nrf2 plays an important role in protecting TBI-induced intestinal mucosal injury, possibly by regulating of inflammatory cytokines and inducing of antioxidant and detoxifying enzymes.
Asunto(s)
Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/metabolismo , Mucosa Intestinal/lesiones , Mucosa Intestinal/metabolismo , Yeyuno/lesiones , Yeyuno/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Apoptosis/fisiología , Permeabilidad de la Membrana Celular/fisiología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Endotoxinas/sangre , Femenino , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Mucosa Intestinal/patología , Yeyuno/patología , Masculino , Ratones , Ratones Endogámicos ICR , Ratones Noqueados , Microvellosidades/patología , Microvellosidades/fisiología , Microvellosidades/ultraestructura , Factor 2 Relacionado con NF-E2/genética , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The neuroprotective effect of N-acetylcysteine (NAC), a sulfhydryl-containing antioxidant, on experimentally induced subarachnoid hemorrhage (SAH) in rats was assessed. NAC was administered to rats after the induction of SAH. Neurological deficits and brain edema were investigated. The activity of antioxidant defense enzymes, copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px), were measured in the brain cortex by spectrophotometer. The content of the lipid peroxidation product malondialdehyde (MDA) was also analyzed. We found that NAC markedly reversed the SAH-induced neurological deficit and brain edema. We further investigated the mechanism involved in the neuroprotective effects of NAC on rat brain tissue and found that NAC significantly increased CuZn-SOD and GSH-Px activity and decreased MDA content in the SAH brain. NAC has the potential to be a novel therapeutic strategy for the treatment of SAH, and its neuroprotective effect may be partly mediated via enhancing the activity of endogenous antioxidant enzymes and inhibiting free radical generation.
Asunto(s)
Carnosina/análogos & derivados , Fármacos Neuroprotectores/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/fisiopatología , Análisis de Varianza , Animales , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/etiología , Carnosina/administración & dosificación , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/etiología , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismoRESUMEN
Ketone bodies have been shown to be favorable alternative metabolic substrates and are protective under neuropathologies. At the same time, cytochrome c release has been reported following traumatic brain injury (TBI) and precipitates apoptosis via the mitochondrial pathway. The present study investigated the effects of a ketogenic diet (KD) on TBI. TBI was produced using the Feeney weight-drop model and the animals were fed either normal diet (ND) or KD. Brain edema was estimated by wet/dry weight ratio; cytochrome c was detected by Western blotting; cellular apoptosis in the penumbra area was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and active caspase-3 immunohistochemical staining. The results show that brain edema, cytochrome c release, and cellular apoptosis were induced after TBI and that KD reduced these changes dramatically. These findings suggest that KD has potential therapeutic benefit in TBI.
Asunto(s)
Apoptosis , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Citocromos c/metabolismo , Dieta Cetogénica , Ácido 3-Hidroxibutírico/sangre , Animales , Glucemia , Encéfalo/enzimología , Encéfalo/patología , Lesiones Encefálicas/sangre , Lesiones Encefálicas/enzimología , Caspasa 3/metabolismo , Activación Enzimática , Immunoblotting , Etiquetado Corte-Fin in Situ , Masculino , Ratas , Ratas Sprague-Dawley , Agua/metabolismoRESUMEN
Hemangiopericytomas, which are more aggressive than meningiomas, are rare in the central nervous system (CNS). We analyzed the clinical, radiological and histological features and treatment of 26 patients with hemangiopericytomas in the CNS. The ratio of male to female patients was 1:1. Most tumors were located in the parasagittal and falx regions. The tumors were dense or mixed as assessed by CT scans, and most were homogeneously enhanced. Most tumors were isointense on T1-weighted MRI, and high or mixed intensity on T2-weighted MRI; they were homogeneously or heterogeneously enhanced. Histological examination indicated numerous small vascular spaces in the tumor. All tumors were immunohistochemically positive for vimentin. All patients were treated with surgery, and some of them underwent subsequent radiotherapy. The recurrence rate for hemangiopericytoma in this study was high. Our observations suggest that the biological behavior of hemangiopericytoma differs markedly from that of meningioma. Surgical removal and post-operative radiotherapy are thus critical for the treatment of this tumor.