RESUMEN
Postnatal subventricular zone (SVZ) neural stem cells generate forebrain glia, namely astrocytes and oligodendrocytes. The cues necessary for this process are unclear, despite this phase of brain development being pivotal in forebrain gliogenesis. Galectin-3 (Gal-3) is increased in multiple brain pathologies and thereby regulates astrocyte proliferation and inflammation in injury. To study the function of Gal-3 in inflammation and gliogenesis, we carried out functional studies in mouse. We overexpressed Gal-3 with electroporation and using immunohistochemistry surprisingly found no inflammation in the healthy postnatal SVZ. This allowed investigation of inflammation-independent effects of Gal-3 on gliogenesis. Loss of Gal-3 function via knockdown or conditional knockout reduced gliogenesis, whereas Gal-3 overexpression increased it. Gal-3 overexpression also increased the percentage of striatal astrocytes generated by the SVZ but decreased the percentage of oligodendrocytes. These novel findings were further elaborated with multiple analyses demonstrating that Gal-3 binds to the bone morphogenetic protein receptor one alpha (BMPR1α) and increases bone morphogenetic protein (BMP) signaling. Conditional knockout of BMPR1α abolished the effect of Gal-3 overexpression on gliogenesis. Gain-of-function of Gal-3 is relevant in pathological conditions involving the human forebrain, which is particularly vulnerable to hypoxia/ischemia during perinatal gliogenesis. Hypoxic/ischemic injury induces astrogliosis, inflammation and cell death. We show that Gal-3 immunoreactivity was increased in the perinatal human SVZ and striatum after hypoxia/ischemia. Our findings thus show a novel inflammation-independent function for Gal-3; it is necessary for gliogenesis and when increased in expression can induce astrogenesis via BMP signaling.
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Astrocitos/metabolismo , Galectina 3/metabolismo , Ventrículos Laterales/citología , Neuroglía/metabolismo , Animales , Diferenciación Celular/fisiología , Movimiento Celular/fisiología , Ventrículos Cerebrales/citología , Regulación de la Expresión Génica , Isquemia/metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos , Células-Madre Neurales/metabolismo , Neurogénesis/fisiología , Oligodendroglía/metabolismoRESUMEN
Traumatic brain injury is an important cause of global morbidity and mortality. After an initial injury, there is a cascade of cellular and molecular events that ultimately lead to cell death. Therapies aim to both counteract these mechanisms and replenish the lost cell population in order to improve recovery. The adult mammal brain has at least two neurogenic regions that maintain physiological functions: the subgranular zone of the dentate gyrus in the hippocampus, which produces neurons that integrate locally, and the subventricular zone (SVZ) adjacent to the lateral ventricles, which produces neuroblasts that migrate through the rostral migratory stream (RMS) to the olfactory bulbs. Brain injuries, as well as neurodegenerative diseases, induce the SVZ to respond by increasing cell proliferation and migration to the injured areas. Here we report that cells migrate from the SVZ and RMS to the injured cortex after traumatic brain injury in mice, and that the physiological RMS migration is not impaired. We also show that Prokineticin 2 (PROK2), a chemokine important for the olfactory bulb neurogenesis, expressed exclusively by cortical microglia in the cortex as early as 24â¯h after injury. We then show that administration of a PROK2 receptor antagonist decreases the number of SVZ cells that reach the injured cortex, while injection of recombinant PROK2 into the cortex of uninjured mice attracts SVZ cells. We also demonstrate that cells expressing PROK2 in vitro directionally attract SVZ cells. These data suggest that PROK2 could be utilized in regeneration efforts for the acutely injured mammalian cortex.
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Lesiones Traumáticas del Encéfalo/terapia , Movimiento Celular/fisiología , Hormonas Gastrointestinales/metabolismo , Ventrículos Laterales/metabolismo , Células-Madre Neurales/metabolismo , Neuropéptidos/metabolismo , Animales , Proliferación Celular/fisiología , Modelos Animales de Enfermedad , Masculino , Ratones Endogámicos C57BL , Microglía/metabolismo , Neurogénesis/fisiologíaRESUMEN
Stem cell transplantation is a promising strategy to treat brain injuries. However, cell-based therapies are limited because poor local cell engraftment. Here, we present a polylactic acid (PLA) scaffold to support mesenchymal stem cells (MSCs) delivery in stroke. We isolated bone marrow MSCs from adult C57/Bl6 mice, cultured them on PLA polymeric rough microfibrous (PRM) scaffolds obtained by rotary jet spinning, and transplanted over the brains of adult C57/Bl6 mice, carrying thermocoagulation-induced cortical stroke. No inflammatory response to PRM was found. MSCs transplantation significantly reduced the area of the lesion and PRM delivery increased MSCs retention at the injury site. In addition, PRM upregulated α6-integrin and CXCL12 production, which may be the cause for greater cell retention at the lesion site and may provide additional benefit to MSCs transplantation procedures. We conclude that PRM scaffolds offer a promising new system to deliver stem cells to injured areas of the brain.
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Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Sistemas de Liberación de Medicamentos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Nanofibras/química , Andamios del Tejido/química , Traumatismos del Sistema Nervioso/terapia , Animales , Células de la Médula Ósea/citología , Diferenciación Celular , Femenino , Ratones , Ratones Endogámicos C57BL , Ingeniería de TejidosRESUMEN
Multiple sclerosis (MS) frequently starts near the lateral ventricles, which are lined by subventricular zone (SVZ) progenitor cells that can migrate to lesions and contribute to repair. Because MS-induced inflammation may decrease SVZ proliferation and thus limit repair, we studied the role of galectin-3 (Gal-3), a proinflammatory protein. Gal-3 expression was increased in periventricular regions of human MS in post-mortem brain samples and was also upregulated in periventricular regions in a murine MS model, Theiler's murine encephalomyelitis virus (TMEV) infection. Whereas TMEV increased SVZ chemokine (CCL2, CCL5, CCL, and CXCL10) expression in wild type (WT) mice, this was inhibited in Gal-3(-/-) mice. Though numerous CD45+ immune cells entered the SVZ of WT mice after TMEV infection, their numbers were significantly diminished in Gal-3(-/-) mice. TMEV also reduced neuroblast and proliferative SVZ cell numbers in WT mice but this was restored in Gal-3(-/-) mice and was correlated with increased numbers of doublecortin+ neuroblasts in the corpus callosum. In summary, our data showed that loss of Gal-3 blocked chemokine increases after TMEV, reduced immune cell migration into the SVZ, reestablished SVZ proliferation and increased the number of progenitors in the corpus callosum. These results suggest Gal-3 plays a central role in modulating the SVZ neurogenic niche's response to this model of MS.
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Encéfalo/metabolismo , Galectina 3/metabolismo , Esclerosis Múltiple/metabolismo , Enfermedad Autoinmune Experimental del Sistema Nervioso/metabolismo , Neurogénesis , Nicho de Células Madre/fisiología , Adolescente , Adulto , Anciano , Animales , Encéfalo/inmunología , Encéfalo/patología , Movimiento Celular , Niño , Femenino , Galectina 3/genética , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Enfermedad Autoinmune Experimental del Sistema Nervioso/inmunología , Enfermedad Autoinmune Experimental del Sistema Nervioso/patología , Células-Madre Neurales/metabolismo , Células-Madre Neurales/patología , Poliomielitis/metabolismo , Poliomielitis/patología , Theilovirus , Adulto JovenRESUMEN
BACKGROUND: Cuprizone leads to demyelination of the corpus callosum (CC) and activates progenitor cells in the adjacent subventricular zone (SVZ), a stem cell niche which contributes to remyelination. The healthy SVZ contains semi-activated microglia and constitutively expresses the pro-inflammatory molecule galectin-3 (Gal-3) suggesting the niche uniquely regulates inflammation. METHODS: We studied the inflammatory response to cuprizone in the SVZ and CC in Gal-3 knockout mice using immunohistochemistry and with the in vitro neurosphere assay. RESULTS: Cuprizone caused loss of myelin basic protein (MBP) immunofluorescence in the CC suggesting demyelination. Cuprizone increased the density of CD45+/Iba1+ microglial cells and also increased Gal-3 expression in the CC. Surprisingly, the number of Gal-3+ and CD45+ cells decreased in the SVZ after cuprizone, suggesting inflammation was selectively reduced therein. Inflammation can regulate SVZ proliferation and indeed the number of phosphohistone H3+ (PHi3+) cells decreased in the SVZ but increased in the CC in both genotypes after cuprizone treatment. BrdU+ SVZ cell numbers also decreased in the SVZ after cuprizone, and this effect was significantly greater at 3 weeks in Gal-3 (-/-) mice compared to WT, suggesting Gal-3 normally limits SVZ cell emigration following cuprizone treatment. CONCLUSIONS: This study reveals a uniquely regulated inflammatory response in the SVZ and shows that Gal-3 participates in remyelination in the cuprizone model. This contrasts with more severe models of demyelination which induce SVZ inflammation and suggests the extent of demyelination affects the SVZ neurogenic response.
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Cuprizona/toxicidad , Enfermedades Desmielinizantes , Inflamación/etiología , Ventrículos Laterales/patología , Inhibidores de la Monoaminooxidasa/toxicidad , Animales , Animales Recién Nacidos , Proteínas de Unión al Calcio/metabolismo , Proliferación Celular/efectos de los fármacos , Cuerpo Calloso/efectos de los fármacos , Cuerpo Calloso/patología , Enfermedades Desmielinizantes/inducido químicamente , Enfermedades Desmielinizantes/complicaciones , Enfermedades Desmielinizantes/patología , Modelos Animales de Enfermedad , Femenino , Galectina 3/deficiencia , Galectina 3/genética , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Masculino , Ratones , Ratones Transgénicos , Proteínas de Microfilamentos/metabolismo , Bulbo Olfatorio/efectos de los fármacos , Bulbo Olfatorio/patología , Oligodendroglía/efectos de los fármacos , Oligodendroglía/metabolismoRESUMEN
Intraoral scans became part of the virtual planning in Dentistry. In the new scenario of digital workflows, dental clinics and laboratories had to establish an online communication that requires the compression, decompression, and transmission of 3D files. Knowledge about the effects of these procedures on the dimensional properties of the files is fundamental to ensure a more realistic virtual planning. The aim of this study was to assess the influence of 3D file compression, decompression, and online transmission on the dimensional properties of dental models from intraoral scanning. Intraoral scan files in.stl format of 50 patients were selected from the database of a dental radiology clinic, with 25 of these patients with mixed dentition and 25 with permanent dentition. The maxilla and mandible scans of each patient were included in the study, generating a total of 100 files. A folder with the 100 files was created and replicated six times with different labels (A, B, C, D, E, F), totaling a sample number of 600 files. Folder A was compressed by WinZip and then decompressed. Folder B went through the same process, but the step of compression and decompression by WinZip was repeated 10 times. The folders C, D, E, F were sent, respectively, through the platforms WeTransfer, Dropbox, Google Drive, and OneDrive, then each of them was downloaded in their respective platforms. After the six folders went through the compression process and were sent by the platforms, each file in the folder was compared with its original file by superimposing the 3D images and identifying the dimensional deviation in the compressed file in relation to the original file. We observed that there were no differences between the six groups regarding dimensional changes from the compression, decompression and online transmission processes. The lack of dimensional changes was observed for the sets of permanent and deciduous. teeth We concluded that it is possible to compress, decompress, and transfer.stl format files online without causing dimensional distortions in the 3D model.
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Imagenología Tridimensional , Registros , Descompresión , Humanos , Imagenología Tridimensional/métodos , Mandíbula , MaxilarRESUMEN
The effects of neuroinvasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) become clinically relevant due to the numerous neurological symptoms observed in Corona Virus Disease 2019 (COVID-19) patients during infection and post-COVID syndrome or long COVID. This study reports the biofabrication of a 3D bioprinted neural-like tissue as a proof-of-concept platform for a more representative study of SARS-CoV-2 brain infection. Bioink is optimized regarding its biophysical properties and is mixed with murine neural cells to construct a 3D model of COVID-19 infection. Aiming to increase the specificity to murine cells, SARS-CoV-2 is mouse-adapted (MA-SARS-CoV-2) in vitro, in a protocol first reported here. MA-SARS-CoV-2 reveals mutations located at the Orf1a and Orf3a domains and is evolutionarily closer to the original Wuhan SARS-CoV-2 strain than SARS-CoV-2 used for adaptation. Remarkably, MA-SARS-CoV-2 shows high specificity to murine cells, which present distinct responses when cultured in 2D and 3D systems, regarding cell morphology, neuroinflammation, and virus titration. MA-SARS-CoV-2 represents a valuable tool in studies using animal models, and the 3D neural-like tissue serves as a powerful in vitro platform for modeling brain infection, contributing to the development of antivirals and new treatments for COVID-19.
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COVID-19 , SARS-CoV-2 , Animales , Encéfalo , COVID-19/complicaciones , Humanos , Ratones , Neuronas , Síndrome Post Agudo de COVID-19RESUMEN
Repairing the human brain remains a challenge, despite the advances in the knowledge of inflammatory response to injuries and the discovery of adult neurogenesis. After brain injury, the hostile microenvironment and the lack of structural support for neural cell repopulation, anchoring, and synapse formation reduce successful repair chances. In the past decade, we witnessed the rise of studies regarding bioscaffolds' use as support for neuro repair. A variety of natural and synthetic materials is available and have been used to replace damaged tissue. Bioscaffolds can assume different shapes and may or may not carry a diversity of content, such as stem cells, growth factors, exosomes, and si/miRNA that promote specific therapeutic effects and stimulate brain repair. The use of these external bioscaffolds and the creation of cell platforms provide the basis for tissue engineering. More recently, researchers were able to engineer brain organoids, neural networks, and even 3D printed neural tissue. The challenge in neural tissue engineering remains in the fabrication of scaffolds with precisely controlled topography and biochemical cues capable of directing and controlling neuronal cell fate. The purpose of this review is to highlight the existing research in the growing field of bioscaffolds' development and neural tissue engineering. Moreover, this review also draws attention to emerging possibilities and prospects in this field.
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Astrocytes are glial cells with an essential role in the central nervous system (CNS), including neuronal support and functionality. These cells also respond to neural injuries and act to protect the tissue from degenerative events. In vitro studies of astrocytes' functionality are important to elucidate the mechanisms involved in such events and contribute to developing therapies to treat neurological disorders. This protocol describes a method to biofabricate a neural-like tissue structure rich in astrocytes by 3D bioprinting astrocytes-laden bioink. An extrusion-based 3D bioprinter was used in this work, and astrocytes were extracted from C57Bl/6 mice pups' brain cortices. The bioink was prepared by mixing cortical astrocytes from up to passage 3 to a biomaterial solution composed of gelatin, gelatin-methacryloyl (GelMA), and fibrinogen, supplemented with laminin, which presented optimal bioprinting conditions. The 3D bioprinting conditions minimized cell stress, contributing to the high viability of the astrocytes during the process, in which 74.08% ± 1.33% of cells were viable right after bioprinting. After 1 week of incubation, the viability of astrocytes significantly increased to 83.54% ± 3.00%, indicating that the 3D construct represents a suitable microenvironment for cell growth. The biomaterial composition allowed cell attachment and stimulated astrocytic behavior, with cells expressing the specific astrocytes marker glial fibrillary acidic protein (GFAP) and possessing typical astrocytic morphology. This reproducible protocol provides a valuable method to biofabricate 3D neural-like tissue rich in astrocytes that resembles cells' native microenvironment, useful to researchers that aim to understand astrocytes' functionality and their relation to the mechanisms involved in neurological diseases.
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Bioimpresión , Animales , Astrocitos , Gelatina , Ratones , Impresión Tridimensional , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site. We show that DCX+ neuroblasts do not penetrate a CSPG-rich injured area probably due to Nogo receptor activation and RhoA/ROCK signaling pathway as we demonstrate in vitro with neural stem cells cultured as neurospheres and pull-down for RhoA. Furthermore, CS-impaired cell migration in vitro induced the formation of large mature adhesions and altered cell protrusion dynamics. ROCK inhibition restored migration in vitro as well as decreased adhesion size.
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Movimiento Celular/efectos de los fármacos , Sulfatos de Condroitina/farmacología , Células-Madre Neurales/citología , Células-Madre Neurales/enzimología , Quinasas Asociadas a rho/metabolismo , Animales , Adhesión Celular/efectos de los fármacos , Extensiones de la Superficie Celular/efectos de los fármacos , Extensiones de la Superficie Celular/metabolismo , Células Cultivadas , Proteína Doblecortina , Activación Enzimática/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Células-Madre Neurales/efectos de los fármacos , Quinasas Asociadas a rho/antagonistas & inhibidores , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
Recruiting neural stem cell (NSC) at the lesion site is essential for central nervous system repair. This process could be triggered by the local delivery of the chemokine SDF-1. We compared two PLGA formulations for local brain SDF-1 delivery: SDF-1 loaded microspheres (MS) and SDF-1 loaded nanoparticles (NP). Both formulations were able to encapsulate more than 80% of SDF-1 but presented different release profiles, with 100% of SDF-1 released after 6days for the MS and with 25% of SDF-1 released after 2 weeks for NP. SDF-1 bioactivity was demonstrated by a chemotactic assay. When injected in mouse brain after traumatic brain injury, only SDF-1 nanoparticles induced NSC migration to the damage area. More neuroblasts (DCX+ cells) could be visualized around the lesions treated with NP SDF-1 compared to the other conditions. Rostral migratory stream destabilization with massive migration of DCX+ cell toward the perilesional area was observed 2 weeks after NP SDF-1 injection. Local injection of SDF-1-loaded nanoparticles induces recruitment of NSC and could be promising for brain injury lesion.
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Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/administración & dosificación , Quimiocina CXCL12/administración & dosificación , Nanopartículas/administración & dosificación , Células-Madre Neurales/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Química Farmacéutica/métodos , Proteína Doblecortina , Femenino , Ratones , Ratones Endogámicos C57BL , MicroesferasRESUMEN
Brain injuries are often associated with the later development of epilepsy. Evidence suggests that morphological and functional changes occur in the remaining neural tissue during a silent (or latent) period in which no seizures are expressed. It is believed that this silent (reorganization) period may provide a therapeutic window for modifying the natural history of disease progression. Here we provide evidence that biperiden, a muscarinic anticholinergic agent, is able to alter disease progression in an animal model of epilepsy. We observed that biperiden was capable of slowing the manifestation of the first spontaneous epileptic seizure and effectively reduced the severity and number of recurrent, spontaneous epileptic seizures during the animals' lifespan. Biomolecular (microdialysis) and electrophysiological (extracellular field recordings) studies determined that biperiden was capable of elevating the threshold of hippocampal excitability, thereby making the hippocampal glutamatergic pathways less responsive to stimuli when high concentrations of potassium were used in vivo or in vitro. Notably, there was no hindrance of long-term memory or learning (a potential problem given the amnestic nature of biperiden). We conclude that biperiden has antiepileptogenic potential and may represent an opportunity for the prevention of post-traumatic epilepsy.
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Biperideno/uso terapéutico , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Agonistas Muscarínicos/toxicidad , Antagonistas Muscarínicos/uso terapéutico , Pilocarpina/toxicidad , Potenciales de Acción/efectos de los fármacos , Animales , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/fisiopatología , Enfermedad Crónica , Citocinas/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Epilepsia/patología , Conducta Exploratoria/efectos de los fármacos , Ácido Glutámico/metabolismo , Hipocampo/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratas , Ratas Wistar , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Traumatic brain injury (TBI) is common in both civilian and military life, placing a large burden on survivors and society. However, with the recognition of neural stem cells in adult mammals, including humans, came the possibility to harness these cells for repair of damaged brain, whereas previously this was thought to be impossible. In this review, we focus on the rodent adult subventricular zone (SVZ), an important neurogenic niche within the mature brain in which neural stem cells continue to reside. We review how the SVZ is perturbed following various animal TBI models with regards to cell proliferation, emigration, survival, and differentiation, and we review specific molecules involved in these processes. Together, this information suggests next steps in attempting to translate knowledge from TBI animal models into human therapies for TBI.
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BACKGROUND AND OBJECTIVES: Computer vision extracts features or attributes from images improving diagnosis accuracy and aiding in clinical decisions. This study aims to investigate the feasibility of using texture analysis of periapical radiograph images as a tool for dental implant treatment planning. METHODS: Periapical radiograph images of 127 jawbone sites were obtained before and after implant placement. From the superimposition of the pre- and post-implant images, four regions of interest (ROI) were delineated on the pre-implant images for each implant site: mesial, distal and apical peri-implant areas and a central area. Each ROI was analysed using Matlab® software and seven image attributes were extracted: mean grey level (MGL), standard deviation of grey levels (SDGL), coefficient of variation (CV), entropy (En), contrast, correlation (Cor) and angular second moment (ASM). Images were grouped by bone types-Lekholm and Zarb classification (1,2,3,4). Peak insertion torque (PIT) and resonance frequency analysis (RFA) were recorded during implant placement. Differences among groups were tested for each image attribute. Agreement between measurements of the peri-implant ROIs and overall ROI (peri-implant + central area) was tested, as well as the association between primary stability measures (PIT and RFA) and texture attributes. RESULTS: Differences among bone type groups were found for MGL (p = 0.035), SDGL (p = 0.024), CV (p < 0.001) and En (p < 0.001). The apical ROI showed a significant difference from the other regions for all attributes, except Cor. Concordance correlation coefficients were all almost perfect (ρ > 0.93), except for ASM (ρ = 0.62). Texture attributes were significantly associated with the implant stability measures. CONCLUSION: Texture analysis of periapical radiographs may be a reliable non-invasive quantitative method for the assessment of jawbone and prediction of implant stability, with potential clinical applications.
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Implantes Dentales , Planificación de Atención al Paciente , Radiografía Dental , HumanosRESUMEN
Intense activation of neurons triggers the appearance of immediate expression genes, including c-Fos. This gene is related to various signal cascades involved in biochemical processes such as neuronal plasticity, cell growth and mitosis. Here we investigate the expression pattern and the refractory period of c-Fos in rats and monkey's brains after stimulation with pentylenetetrazol. Rats and monkeys were sacrificed at various times after PTZ-induced seizure. Here we show that rats and monkeys already showed c-Fos expression at 0.5 h after seizure. Yet, the pattern of protein expression was longer in monkeys than rats, and also was not uniform (relative intensity) across different brain regions in monkeys as opposed to rats. In addition monkeys had a regional brain variation with regard to the temporal profile of c-Fos expression, which was not seen in rats. The refractory period after a second PTZ stimulation was also markedly different between rats and monkeys with the latter even showing a summatory effect on c-Fos expression after a second stimulation. However, assessment of c-Fos mRNA in rats indicated a post-transcriptional control mechanism underlying the duration of the refractory period. The difference in the protein expression pattern in rodents and primates characterizes a functional aspect of brain biochemistry that differs between these mammalian orders and may contribute for the more developed primate cognitive complexity as compared to rodents given c-Fos involvement in cognitive and learning tasks.
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Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site. We show that DCX+ neuroblasts do not penetrate a CSPG-rich injured area probably due to Nogo receptor activation and RhoA/ROCK signaling pathway as we demonstrate in vitro with neural stem cells cultured as neurospheres and pull-down for RhoA. Furthermore, CS-impaired cell migration in vitro induced the formation of large mature adhesions and altered cell protrusion dynamics. ROCK inhibition restored migration in vitro as well as decreased adhesion size.
RESUMEN
Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site. We show that DCX+ neuroblasts do not penetrate a CSPG-rich injured area probably due to Nogo receptor activation and RhoA/ROCK signaling pathway as we demonstrate in vitro with neural stem cells cultured as neurospheres and pull-down for RhoA. Furthermore, CS-impaired cell migration in vitro induced the formation of large mature adhesions and altered cell protrusion dynamics. ROCK inhibition restored migration in vitro as well as decreased adhesion size.
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OBJETIVO: mapear os fluxos de trabalho (processos) da FO-UFG relativos ao atendimento ao paciente, incluindo aspectos administrativos, atendimento clínico, ensino, pesquisa e extensão, identificando onde e quais recursos computacionais seriam introduzidos. MÉTODO: Entrevistas exploratórias/ouvidoria com informantes-chave foram realizadas. Essas informações foram registradas utilizando a notação BPMN (Bussines Process Modeling Notation). RESULTADOS: Foram obtidos 15 fluxos de trabalho, distribuídos em 4 categorias: disponibilização de vagas, agendamento, movimentação de prontuários e faturamento. Três módulos de um sistema computacional do Hospital das Clínicas-UFG foram adaptados e utilizados para otimizar a realização dos fluxos mapeados, bem como o sistema de regulação da Secretaria Municipal de Saúde de Goiânia-GO. CONCLUSÃO: Apesar da incipiente implementação desses processos não permitir uma avaliação dos impactos, acreditamos num aprimoramento da gestão da informação, integração com SUS, melhoria da qualidade da assistência à saúde e reorientação da formação do estudante da FO-UFG, segundo as Diretrizes Curriculares Nacionais.
OBJECTIVE: to map the workflows (processes) of the FO-UFG relating to patient care, including administrative aspects, clinical care, teaching, research and extension, identifying where and what computer resources would be introduced. METLHOD: Exploratory interviews / ombudsman with key informants was held. These data were recordedusing BPMN (Bussines Process Modeling Notation). RESULTS: We obtained 15 workflows, distributed in four categories: availability of jobs, scheduling, handling of patient records and billing. Three modules of a computer system at the Hospital das Clinicas-UFG have been adapted and used to optimize the performance of flows mapped, and the systemof regulation of the Secretariat of Health of Goiânia-GO. CONCLUSION: Despite the incipient implementation of these processes do not allow an assessment of impacts, we believe in improvement of information management, integration with SUS, improving the quality of health care, reorientation of the educational experience of the FO-UFG, accordingto National Curriculum Guidelines.
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Humanos , Sistemas de Registros Médicos Computarizados , Informática Odontológica , Flujo de Trabajo , Congresos como Asunto , OdontologíaRESUMEN
Objetivo: O objetivo do estudo foi analisar decisões colegiadas publicadas pelo Tribunal de Justiça de Goiás (TJGO) de ações instauradas contra prestadores de serviço que emitiram resultado falso-positivo em teste para HIV. Material e método: Procedeu-se pesquisa no banco de dados do TJGO, buscando acórdãos de apelação civil cujos inteiros teores contemplassem o escopo do trabalho (onze acórdãos foram encontrados). Resultados: Observou-se que resultados falso-positivos decorriam de exames de triagem para HIV (100%). Os pacientes não foram informados sobre a possibilidade de falso-positivo (54,5%), gerandoa lide. O dano moral foi solicitado em todas as ações, sendo julgado procedente em 54,5% em 1ª instância e em 72,7%, em 2ª instância, com valor médio condenatório de R$25.000,00 nestas. A responsabilidade civil foi considerada objetiva em 75% das ações que resultaram em condenação em 2ª instância. Conclusão: Conclui-se que os danos morais e materiais decorrentes do diagnóstico errôneo de HIV têm sido judicialmente requeridos com tendência de condenação em primeira instância e de manutenção dessa sentença em 2ª instância.
Aim: The aim of the study was to analyze collective decisions published by the Goiás Court of Justice (TJGO) of lawsuits brought against service providers who issued false positive result on HIV test. Materials and methods: The search was proceeded into TJGO database, seeking civil appellate judgments whose entire contents contemplate the scope of the study (eleven judgments were found). Results: It was noted that false-positive results resulted from screening tests for HIV (100%). Patients were not informed about the possibility of false-positive (54.5%), generating the judicial action. The moral damage has been requested in all actions, being upheld at 54.5% in 1st instance and 72.7% in the 2nd instance, with average damning value of R$ 25,000,00. The civil liability was considered objective in 75% of the actions that resulted in conviction in 2nd instance. Conclusion: It was concluded that the moral and materialdamages arising from erroneous diagnosis of HIV have been legally required and present a trend towards conviction at first instance and maintenance of this trial in the 2nd instance.