RESUMO
Neurulation is a crucial process in the formation of the central nervous system (CNS), which begins with the folding and fusion of the neural plate, leading to the generation of the neural tube and subsequent development of the brain and spinal cord. Environmental and genetic factors that interfere with the neurulation process promote neural tube defects (NTDs). Connexins (Cxs) are transmembrane proteins that form gap junctions (GJs) and hemichannels (HCs) in vertebrates, allowing cell-cell (GJ) or paracrine (HCs) communication through the release of ATP, glutamate, and NAD+; regulating processes such as cell migration and synaptic transmission. Changes in the state of phosphorylation and/or the intracellular redox potential activate the opening of HCs in different cell types. Cxs such as Cx43 and Cx32 have been associated with proliferation and migration at different stages of CNS development. Here, using molecular and cellular biology techniques (permeability), we demonstrate the expression and functionality of HCs-Cxs, including Cx46 and Cx32, which are associated with the release of ATP during the neurulation process in Xenopus laevis. Furthermore, applications of FGF2 and/or changes in intracellular redox potentials (DTT), well known HCs-Cxs modulators, transiently regulated the ATP release in our model. Importantly, the blockade of HCs-Cxs by carbenoxolone (CBX) and enoxolone (ENX) reduced ATP release with a concomitant formation of NTDs. We propose two possible and highly conserved binding sites (N and E) in Cx46 that may mediate the pharmacological effect of CBX and ENX on the formation of NTDs. In summary, our results highlight the importance of ATP release mediated by HCs-Cxs during neurulation.
Assuntos
Conexinas , Defeitos do Tubo Neural , Animais , Conexinas/metabolismo , Neurulação , Junções Comunicantes/metabolismo , Tubo Neural/metabolismo , Defeitos do Tubo Neural/metabolismo , Trifosfato de Adenosina/metabolismoRESUMO
PURPOSE: One of the most common malformations of the central nervous system is related to embryonic neural tube alterations. We hypothesized that anencephaly affects the development of the vagina during the human second trimester of pregnancy. Our study compared the biometric parameters of the vagina in human female fetuses with neural tube defects. METHODS: In our study, 34 female fetuses were analyzed, 22 normal and 12 anencephalic, aged between 12 and 22 weeks post conception (WPC). After dissection of the pelvis and individualization of the genital tract, we evaluated the length and width of the vagina using the Image J software. We compared the means statistically using the Wilcoxon-Mann-Whitney test and performed linear regression. RESULTS: We do not identify statistical significance between the groups for the measurements of vaginal length (Control 3.12-18.33 mm/mean = 9.08 mm/SD + - 3.77 vs. Anencephalic 2.91-13.10 mm/mean = 7.24 mm/SD + - 2.28, p = 0.3469) and vaginal width (Control 1.04-4.86 mm/mean = 2.71 mm/SD + - 0.94 vs. Anencephalic 1.35-3.17 mm/mean = 2.13 mm/SD + - 0.65; p = 0.2503). The linear regression analysis indicated that 78.57% significance was found in the correlations in normocephalic fetuses and 57.14% significance in anencephalic fetuses (12.3-18.6 WPC). CONCLUSIONS: We do not find differences in the length and width of the vagina in anencephalic fetuses but the vaginal length and width shows a lesser tendency of growth in the anencephalic fetuses during the second trimester suggesting that anencephaly can impact the development of the vagina.
Assuntos
Anencefalia , Defeitos do Tubo Neural , Vagina , Feminino , Feto , Humanos , Lactente , Tubo Neural/embriologia , Defeitos do Tubo Neural/complicações , Gravidez , Segundo Trimestre da GravidezRESUMO
Introducción: Los quistes neuroentéricos son lesiones congénitas, benignas, solitarias e infrecuentes del eje espinal, compuestas de tejido endodérmico heterotópico, productos del cierre incompleto del tubo neural. Se presentan, principalmente, en hombres durante la primera y segunda década de vida. Se localizan mayoritariamente en el espacio intradural/extramedular, ventralmente a la médula espinal, a nivel cervical bajo o torácico superior. La sintomatología neurológica depende de la localización del quiste. El diagnóstico presuntivo se realiza con una resonancia magnética, y el definitivo con un estudio histopatológico, llevado a cabo posterior a la exéresis completa o parcial de la muestra, con abordaje posterior, en la mayoría de los casos. Caso: Se describe el caso de una paciente de 35 años, quien tiene antecedente de haber presentado a los 14 años un quiste neuroentérico intradural/extramedular, a nivel cervial bajo. Había debutado con cervicalgia irradiada a miembros superiores e inferiores, radiculopatía, pérdida de la fuerza muscular, e hiperreflexia. Se realizó en ese momento una resonancia magnética, evidenciando una lesión ocupante de espacio en C5 y C6, la cual fue intervenida quirúrgicamente a través de una laminectomía en C5-C6 con abordaje posterior. Se realizó exéresis completa de la misma. El estudio anatomopatológico reportó quiste neuroentérico intradural/extramedular, sin atipias celulares. La evolución posoperatoria de la paciente resultó satisfactoria. Conclusión: Se describe este caso clínico, resaltando su importancia, al tratarse de lesiones sumamente infrecuentes en la literatura médica, con sintomatología poco específica, pudiendo confundirse con otras patologías, y recidivar, incluso después de haberse extraído completamente
Introduction: Neuroenteric cysts are congenital, benign, solitary, and infrequent lesions of the spinal axis, composed of heterotopic endodermic tissue, resulting from an incomplete closure of the neural tube. They mainly occur in men, during the first or second decade of life. Most of these cysts are located in the intradural/extramedullary compartment, ventrally to the spinal cord, especially at the lower cervical or upper thoracic spine. The neurological symptomatology varies depending on the location of the cyst. The presumptive diagnosis is made with magnetic resonance imaging, and the definitive diagnosis is made with a histopathological assessment, which is done after a complete or partial resection of the mass, generally with a posterior approach. Case presentation: We describe the case of a 35-year-old female patient, with the medical history of presenting an intradural/extramedullary neuroenteric cyst, located at the lower cervical level, at the age of 14. She presented cervical pain irradiated to upper and lower limbs, radicular pain, loss of muscular strength, and hyperreflexia. A magnetic resonance imaging was indicated, showing a space-occupying lesion at the C5 and C6 levels, which was surgically intervened through a posterior cervical (C5-C6) laminectomy. A complete resection of this mass was performed. The histopathological assessment reported an intradural/extramedullary neuroenteric cyst, with no cellular atypia. The patient's postoperative progress and development were satisfactory. Conclusion: The objective is to describe this case, highlighting its importance, since these lesions are extremely infrequent in the medical literature, with a non-specific symptomatology, which is why they can be confused with other pathologies, and recur, even after their complete resection.
Assuntos
Feminino , Neoplasias , Medula Espinal , Cervicalgia , Tubo Neural , LaminectomiaRESUMO
The internalization of multi-cellular tissues is a key morphogenetic process during animal development and organ formation. A good example of this is the initial stages of vertebrate central nervous system formation whereby a transient embryonic structure called the neural plate is able to undergo collective cell rearrangements within the dorsal midline. Despite the fact that defects in neural plate midline internalization may result in a series of severe clinical conditions, such as spina bifida and anencephaly, the biochemical and biomechanical details of this process remain only partially characterized. Here we review the main cellular and molecular mechanisms underlying midline cell and tissue internalization during vertebrate neural tube formation. We discuss the contribution of collective cell mechanisms including convergence and extension, as well as apical constriction facilitating midline neural plate shaping. Furthermore, we summarize recent studies that shed light on how the interplay of signaling pathways and cell biomechanics modulate neural plate internalization. In addition, we discuss how adhesion-dependent cell-cell contact appears to be a critical component during midline cell convergence and surface cell contraction via cell-cell mechanical coupling. We envision that more detailed high-resolution quantitative data at both cell and tissue levels will be required to properly model the mechanisms of vertebrate neural plate internalization with the hope of preventing human neural tube defects.
Assuntos
Placa Neural , Tubo Neural , Vertebrados/embriologia , Animais , Morfogênese , Placa Neural/embriologia , Tubo Neural/embriologia , NeurulaçãoRESUMO
Background: Malformations are structural or functional abnormalities in the organs and structures present at birth. Theseconditions are rarely described in the newborns of dogs and can lead to their death. Meroanencephaly is a defect of theneural tube closure malformation, a type of anencephaly and results from a failure of closure of the rostral neuropore(neural crest), and consequently the development of the calvary becomes defective. This study aims to characterize theclinical-pathological aspects of neonatal meroanencephaly since brain malformations are rare in newborn dogs.Case: A 2-day-old English Pointer canine was sent for a necropsy. The newborn belonged to a litter of eight puppies, andonly this one had macroscopic cranial alterations. Another puppy that died as a consequence of being trampled by thebitch was also necropsied. The newborn was alive for 48 h until death and presented apathy, crying, sucking reflex andopisthotonus. Macroscopic examination of the baby revealed flattening of the skull, with a slit at the site of bone symphysis fusion, and a slit in the skin of the parietal region, covered by thin, translucent meningeal tissue. The newborn hadno other macroscopic changes. The heads of the two animals were examined by radiography to identify the features ofanencephaly in one of the animals by visualizing skull bone flattening. Upon removing the skin and exposing the cranialcavity, an irregular reddish mass was revealed, that corresponded microscopically to area cerebrovasculosa, composed ofneurons and rudimentary glial tissue, vascular neoformation and, hemorrhage and congestion. The cranial nerves was notpossible to observe. There was disorganization of the brain areas with no limitation of white and gray matter and scarceneurons and also a region similar to the cerebellum, with a molecular layer but without the Purkinje neurons. In the spinal...(AU)
Assuntos
Animais , Cães , Anencefalia/veterinária , Tubo Neural/anormalidades , Crista Neural/anormalidades , Anormalidades Congênitas/veterinária , Animais Recém-NascidosRESUMO
Background: Malformations are structural or functional abnormalities in the organs and structures present at birth. Theseconditions are rarely described in the newborns of dogs and can lead to their death. Meroanencephaly is a defect of theneural tube closure malformation, a type of anencephaly and results from a failure of closure of the rostral neuropore(neural crest), and consequently the development of the calvary becomes defective. This study aims to characterize theclinical-pathological aspects of neonatal meroanencephaly since brain malformations are rare in newborn dogs.Case: A 2-day-old English Pointer canine was sent for a necropsy. The newborn belonged to a litter of eight puppies, andonly this one had macroscopic cranial alterations. Another puppy that died as a consequence of being trampled by thebitch was also necropsied. The newborn was alive for 48 h until death and presented apathy, crying, sucking reflex andopisthotonus. Macroscopic examination of the baby revealed flattening of the skull, with a slit at the site of bone symphysis fusion, and a slit in the skin of the parietal region, covered by thin, translucent meningeal tissue. The newborn hadno other macroscopic changes. The heads of the two animals were examined by radiography to identify the features ofanencephaly in one of the animals by visualizing skull bone flattening. Upon removing the skin and exposing the cranialcavity, an irregular reddish mass was revealed, that corresponded microscopically to area cerebrovasculosa, composed ofneurons and rudimentary glial tissue, vascular neoformation and, hemorrhage and congestion. The cranial nerves was notpossible to observe. There was disorganization of the brain areas with no limitation of white and gray matter and scarceneurons and also a region similar to the cerebellum, with a molecular layer but without the Purkinje neurons. In the spinal...
Assuntos
Animais , Cães , Anencefalia/veterinária , Anormalidades Congênitas/veterinária , Crista Neural/anormalidades , Tubo Neural/anormalidades , Animais Recém-NascidosRESUMO
Neural crest cells (NCCs) comprise a population of multipotent progenitors and stem cells at the origin of the peripheral nervous system (PNS) and melanocytes of skin, which are profoundly influenced by microenvironmental factors, among which is basic fibroblast growth factor 2 (FGF2). In this work, we further investigated the role of this growth factor in quail trunk NC morphogenesis and demonstrated its huge effect in NCC growth mainly by stimulating cell proliferation but also reducing cell death, despite that NCC migration from the neural tube explant was not affected. Moreover, following FGF2 treatment, reduced expression of the early NC markers Sox10 and FoxD3 and improved proliferation of HNK1-positive NCC were observed. Since these markers are involved in the regulation of glial and melanocytic fate of NC, the effect of FGF2 on NCC differentiation was investigated. Therefore, in the presence of FGF2, increased proportions of NCCs positives to the melanoblast marker Mitf as well as NCCs double stained to Mitf and BrdU were recorded. In addition, treatment with FGF2, followed by differentiation medium, resulted in increased expression of melanin and improved proportion of melanin-pigmented melanocytes without alteration in the glial marker Schwann myelin protein (SMP). Taken together, these data further reveal the important role of FGF2 in NCC proliferation, survival, and differentiation, particularly in melanocyte development. This is the first demonstration of FGF2 effects in melanocyte commitment of NC and in the proliferation of Mitf-positive melanoblasts. Elucidating the differentiation process of embryonic NCCs brings us a step closer to understanding the development of the PNS and then undertaking the search for advanced technologies to prevent, or treat, injuries caused by NC-related disorders, also known as neurocristopathies.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células-Tronco Embrionárias/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Melanócitos/efeitos dos fármacos , Crista Neural/efeitos dos fármacos , Animais , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Embrião de Galinha , Células-Tronco Embrionárias/fisiologia , Melaninas/metabolismo , Melanócitos/fisiologia , Crista Neural/citologia , Tubo Neural/citologia , Tubo Neural/efeitos dos fármacos , Nervos Periféricos/citologia , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/fisiologia , Codorniz/embriologia , TroncoRESUMO
Folate deficiency in pregnant has been linked to neural tube defects in a substantial to neural tube defects in a substantial amount of medical literatures and has become a well-known fact among doctors; however, the knowledge of pregnant ladies about this association is poorly evaluated in our community. Vitamin and mineral deficiency is common among people in developing countries;however, the awareness of those people about such deficits and their associating compications is lacking. This study was conducted to evaluate the knowledge, attitude and practice of a cohort of pregnant ladies in Al-Diwaniyiah province in Mid-Euphrates region in Iraq. The present cross sectional study included 30 pregnant ladies. The study started on November 2018 and ended on January 2019. The study was carried out inAl-Diwaniyah maternity and child teaching hospital in Al-Diwaniyah province in Mid-Euphrates region, Iraq. The knowledge, attitude and practice of women regardin folie acid supplementation during early pregnancy was assessed according to 7 knowledge questions, 5 attitude questions and 5 practice questions. These questions and the demopgraphic data concerning women enrolled in the current study were obtained. The results of current study revealed poor knowledge about the advantage of folic acid in preventing congenital abnormalities was very obvious since ost of responses to the 7 questions concerning knowledge domain were within strongy disagreeing, disagree and neutral scores. Majority of response within attitude domain were in the form of disagree and strongly disagree. No correlation was found between any of the demain and the demographic characteristies of the study sample. Current study concluded that in Iraqi community, the knowledge and attitude of women toward the benefit of folie acid during early pregnancy in preventing neural tube defect iis poor; however, they practice well with this regard not due to their knowledge but because of the policy adopted by governmental antenatal care clinics and institutes (AU)
Assuntos
Humanos , Feminino , Gravidez , Estudos Transversais , Estudos de Coortes , Gestantes , Tubo Neural/anormalidades , Ácido Fólico/uso terapêuticoRESUMO
BACKGROUND: The high-density lipoprotein receptor SR-B1 mediates cellular uptake of several lipid species, including cholesterol and vitamin E. During early mouse development, SR-B1 is located in the maternal-fetal interface, where it facilitates vitamin E transport towards the embryo. Consequently, mouse embryos lacking SR-B1 are vitamin E-deficient, and around half of them fail to close the neural tube and show cephalic neural tube defects (NTD). Here, we used transcriptomic profiling to identify the molecular determinants of this phenotypic difference between SR-B1 deficient embryos with normal morphology or with NTD. RESULTS: We used RNA-Seq to compare the transcriptomic profile of three groups of embryos retrieved from SR-B1 heterozygous intercrosses: wild-type E9.5 embryos (WT), embryos lacking SR-B1 that are morphologically normal, without NTD (KO-N) and SR-B1 deficient embryos with this defect (KO-NTD). We identified over 1000 differentially expressed genes: down-regulated genes in KO-NTD embryos were enriched for functions associated to neural development, while up-regulated genes in KO-NTD embryos were enriched for functions related to lipid metabolism. Feeding pregnant dams a vitamin E-enriched diet, which prevents NTD in SR-B1 KO embryos, resulted in mRNA levels for those differentially expressed genes that were more similar to KO-N than to KO-NTD embryos. We used gene regulatory network analysis to identify putative transcriptional regulators driving the different embryonic expression profiles, and identified a regulatory circuit controlled by the androgen receptor that may contribute to this dichotomous expression profile in SR-B1 embryos. Supporting this possibility, the expression level of the androgen receptor correlated strongly with the expression of several genes involved in neural development and lipid metabolism. CONCLUSIONS: Our analysis shows that normal and defective embryos lacking SR-B1 have divergent expression profiles, explained by a defined set of transcription factors that may explain their divergent phenotype. We propose that distinct expression profiles may be relevant during early development to support embryonic nutrition and neural tube closure.
Assuntos
Antígenos CD36/deficiência , Antígenos CD36/genética , Perfilação da Expressão Gênica , Técnicas de Inativação de Genes , Redes Reguladoras de Genes , Tubo Neural/embriologia , Transcrição Gênica , Animais , Humanos , Camundongos , Tubo Neural/metabolismo , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/metabolismo , Fenótipo , DesmameRESUMO
Folate deficiency has been known to contribute to neural tube and neural crest defects, but why these tissues are particularly affected, and which are the molecular mechanisms involved in those abnormalities are important human health questions that remain unanswered. Here we study the function of two of the main folate transporters, FolR1 and Rfc1, which are robustly expressed in these tissues. Folate is the precursor of S-adenosylmethionine, which is the main donor for DNA, protein and RNA methylation. Our results show that knockdown of FolR1 and/or Rfc1 reduced the abundance of histone H3 lysine and DNA methylation, two epigenetic modifications that play an important role during neural and neural crest development. Additionally, by knocking down folate transporter or pharmacologically inhibiting folate transport and metabolism, we observed ectopic Sox2 expression at the expense of neural crest markers in the dorsal neural tube. This is correlated with neural crest associated defects, with particular impact on orofacial formation. By using bisulfite sequencing, we show that this phenotype is consequence of reduced DNA methylation on the Sox2 locus at the dorsal neural tube, which can be rescued by the addition of folinic acid. Taken together, our in vivo results reveal the importance of folate as a source of the methyl groups necessary for the establishment of the correct epigenetic marks during neural and neural crest fate-restriction.
Assuntos
Deficiência de Ácido Fólico/fisiopatologia , Crista Neural/metabolismo , Fatores de Transcrição SOXB1/fisiologia , Animais , Embrião de Galinha , Metilação de DNA/efeitos dos fármacos , Epigênese Genética/genética , Repressão Epigenética/genética , Repressão Epigenética/fisiologia , Epigenômica , Receptor 1 de Folato , Ácido Fólico/metabolismo , Deficiência de Ácido Fólico/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Histonas/metabolismo , Humanos , Tubo Neural/metabolismo , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/fisiopatologiaRESUMO
Introdução: A úlcera por pressão (UPP) é uma das complicações mais comuns em portadores de lesão medular, dos mais graves e frequentes problemas destes pacientes. A incidência e evolução depende dos grupos estudados, tendo as crianças e adolescentes características específicas durante o crescimento. A maior parte das descrições na literatura referem-se a adultos que desenvolveram UPP durante internação. O objetivo é descrever os resultados de pacientes operados para fechamento de úlcera por pressão na unidade de Pediatria do Hospital Sarah Brasília. Métodos: Estudo descritivo, retrospectivo de pacientes operados de 2005 a 2010 devido à lesão por pressão e análise estatística. Resultados: 116 pacientes foram admitidos para tratamento cirúrgico de UPP no Hospital Sarah, sendo 20 (17,2%) internados na Pediatria; 15 (75%) homens e 5 (25%) mulheres, todos provenientes de ambiente comunitário; 60% localizadas na região isquiática; com seguimento de 15 anos; 70% eram portadores de malformação do tubo neural. Os procedimentos cirúrgicos foram indicados para úlcera por pressão grau III e IV. Utilizou-se retalho do músculo glúteo (3), em ilha (8) ou península (3), fechamento primário e coccigectomia; retalho do músculo tensor da fáscia lata. Três casos apresentaram complicações, 65% evoluíram com recidiva e 15% com surgimento de novas lesões na região pélvica. Conclusão: A principal causa de lesão por pressão em Pediatria foi devido à malformação do tubo neural (70%), adquiridas na comunidade, localizadas na região isquiática. Embora estivessem em atendimento no programa de reabilitação, ainda foi observado alto índice de recidivas (65%).
Introduction: Pressure ulcers (PUs), or pressure sores, are among the most common serious complications in patients with spinal cord injury. The incidence and evolution in children and adolescents have specific characteristics. Most prior reports evaluated adults who developed PUs in the hospital. The objective is to describe the outcomes of surgical PU closure in children and adolescents in the Hospital Sarah Brasília pediatric unit. Methods: This was a retrospective statistical analysis of patients who underwent surgery for PUs. Statistical analysis of the incidence of PUs was performed using Epi Info version 3.2.2. Results: Of 116 patients who underwent surgery for PUs at the Hospital Sarah between 2005 and 2010, 20 (17.2%) were admitted to the Pediatric Unit. All 15 (75%) male and 5 (25%) female patients were admitted from a community setting. PUs were located in the ischial region in 60% of patients. The followup period was 15 years. Neural tube malformations were present in 70% of patients. We performed surgery for grade III and IV PUs, using gluteal flaps, primary closure and coccygectomy, and tensor fascia lata flaps. Three cases had complications, 65% developed recurrences, and 15% developed new ulcers in the pelvic region. Conclusion: The main cause of PUs in pediatric cases admitted to the rehabilitation hospital was a neural tube malformation (70%) in the ischial region. Despite admission to the rehabilitation program, a high recurrence rate (65%) was observed.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , História do Século XXI , Pediatria , Reabilitação , Ciática , Procedimentos Cirúrgicos Operatórios , Úlcera , Estudos Retrospectivos , Úlcera por Pressão , Tubo Neural , Pediatria/métodos , Reabilitação/métodos , Ciática/cirurgia , Ciática/terapia , Procedimentos Cirúrgicos Operatórios/métodos , Úlcera/cirurgia , Úlcera por Pressão/cirurgia , Úlcera por Pressão/complicações , Úlcera por Pressão/terapia , Tubo Neural/cirurgiaRESUMO
Introducción: Los quistes epidermoides cerebrales son tumores de origen embrionario presentes desde la formación del tubo neural. Caso clínico: Hombre de 78 años con focalización en hemicuerpoizquierdo TAC cerebral reportó masa frontotemporal que se extirpó quirúrgicamente y el estudio histopatológico confirma diagnóstico de quiste epidermoide. Discusión: Los quistes epidermoides son tumores poco frecuentes y representan menos del 2% de los tumores intracraneales, el angulo cerebelopontino es la ubicación más frecuente y la resección completa junto con toda la cápsula es el único tratamiento efectivo.
Introduction: Epidermoid cysts are tumors of embryonic origin present since the formation of the neural tube. Case report: A 78-year-old male with a left hemisphere, brain CT scan reported frontotemporal mass that was surgically removed and the histopathological study confirmed a diagnosis of epidermoid cyst. Discussion: Epidermoid cysts are rare tumors and account for less than 2% of intracranial tumors, cerebellar angle is the most frequent site, and complete resection with the entire capsule is the only effective treatment.
Assuntos
Humanos , Masculino , Idoso , Cistos , Cisto Epidérmico , Encéfalo , Cápsulas , Doenças do Sistema Nervoso Central , Seleção de Sítio de Tratamento de Resíduos , Tubo NeuralRESUMO
SR-BI is the main receptor for high density lipoproteins (HDL) and mediates the bidirectional transport of lipids, such as cholesterol and vitamin E, between these particles and cells. During early development, SR-BI is expressed in extraembryonic tissue, specifically in trophoblast giant cells in the parietal yolk sac. We previously showed that approximately 50% of SR-BI-/- embryos fail to close the anterior neural tube and develop exencephaly, a perinatal lethal condition. Here, we evaluated the role of SR-BI in embryonic vitamin E uptake during murine neural tube closure. Our results showed that SR-BI-/- embryos had a very low vitamin E content in comparison to SR-BI+/+ embryos. Whereas SR-BI-/- embryos with closed neural tubes (nSR-BI-/-) had high levels of reactive oxygen species (ROS), intermediate ROS levels between SR-BI+/+ and nSR-BI-/- embryos were detected in SR-BI-/- with NTD (NTD SR-BI-/-). Reduced expression of Pax3, Alx1 and Alx3 genes was found in NTD SR-BI-/- embryos. Maternal α-tocopherol dietary supplementation prevented NTD almost completely (from 54% to 2%, p < 0.001) in SR-BI-/- embryos and normalized ROS and gene expression levels. In sum, our results suggest the involvement of SR-BI in the maternal provision of embryonic vitamin E to the mouse embryo during neural tube closure.
Assuntos
Antígenos CD36/deficiência , Desenvolvimento Embrionário , Tubo Neural/embriologia , Tubo Neural/metabolismo , Vitamina E/metabolismo , Animais , Biomarcadores , Suplementos Nutricionais , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Camundongos Knockout , Oxirredução , Saco Vitelino/embriologia , Saco Vitelino/metabolismo , alfa-Tocoferol/administração & dosagemRESUMO
El mielomeningocele es una malformación congénita por defecto del cierre del tubo neural, se produce en las primeras semanas de crecimiento intrauterino. Consiste en una masa quística que incluye tejido nervioso y meninges, acompañadas de una fusión incompleta de los arcos vertebrales. Produce severos daños neurales y puede asociarse a otras malformaciones. Su reparación, en las primeras horas de vida, es necesaria para evitar complicaciones que pueden comprometer la vida del niño o causar mayor discapacidad. Se reportó un caso de un recién nacido con diagnóstico de mielomeningocele fisurado, a nivel lumbar. Se intervino quirúrgicamente en las primeras 6 h de vida; se disecó el saco dural y se separaron las raíces, logrando el cierre completo de la duramadre. Se reparó la piel con afrontamiento de los bordes y adecuada cicatrización de la herida. Fue aplicada antibioticoterapia profiláctica con cefalosporina de tercera generación. El infante egresó a los 10 días de operado sin complicaciones neuroquirúgicas asociadas (AU).
Meningomyelocele is a congenital malformation by defect of neural tube closing, produced in the first weeks of intrauterine grow. It is a cystic mass that includes nervous tissues and meninges, together with an incomplete fusion of the vertebral arches. It produces severe neural damages and could be associated to other malformations. It is necessary to repair it during the first hours after birth to avoid complications that could compromise the childs life or cause more disability. The case of a new-born child diagnosed with fissured meningomyelocele at the lumbar level is presented. He was operated in the first six hours after birth; the dural sac was dissected and the roots separated, reaching the complete dura mater closure. The skin was repaired with edges affronting and adequate wound healing. Prophylactic antibiotic therapy with third generation cephalosporin was applied. The child was discharged 10 days alter the surgery without associated neurosurgical complications (AU).
Assuntos
Humanos , Masculino , Recém-Nascido , Recém-Nascido/fisiologia , Meningomielocele/cirurgia , Meningomielocele/complicações , Meningomielocele/diagnóstico , Meningomielocele/epidemiologia , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Malformações Vasculares do Sistema Nervoso Central/mortalidade , Malformações Vasculares do Sistema Nervoso Central/terapia , Tubo Neural/anormalidades , Medula Espinal/anormalidades , Ácido Fólico/genéticaAssuntos
Humanos , Feminino , Adulto , Diagnóstico por Imagem , Relatos de Casos , Ependimoma , Tubo Neural/lesõesRESUMO
El mielomeningocele es una malformación congénita por defecto del cierre del tubo neural, se produce en las primeras semanas de crecimiento intrauterino. Consiste en una masa quística que incluye tejido nervioso y meninges, acompañadas de una fusión incompleta de los arcos vertebrales. Produce severos daños neurales y puede asociarse a otras malformaciones. Su reparación, en las primeras horas de vida, es necesaria para evitar complicaciones que pueden comprometer la vida del niño o causar mayor discapacidad. Se reportó un caso de un recién nacido con diagnóstico de mielomeningocele fisurado, a nivel lumbar. Se intervino quirúrgicamente en las primeras 6 h de vida; se disecó el saco dural y se separaron las raíces, logrando el cierre completo de la duramadre. Se reparó la piel con afrontamiento de los bordes y adecuada cicatrización de la herida. Fue aplicada antibioticoterapia profiláctica con cefalosporina de tercera generación. El infante egresó a los 10 días de operado sin complicaciones neuroquirúgicas asociadas (AU).
Meningomyelocele is a congenital malformation by defect of neural tube closing, produced in the first weeks of intrauterine grow. It is a cystic mass that includes nervous tissues and meninges, together with an incomplete fusion of the vertebral arches. It produces severe neural damages and could be associated to other malformations. It is necessary to repair it during the first hours after birth to avoid complications that could compromise the child’s life or cause more disability. The case of a new-born child diagnosed with fissured meningomyelocele at the lumbar level is presented. He was operated in the first six hours after birth; the dural sac was dissected and the roots separated, reaching the complete dura mater closure. The skin was repaired with edges affronting and adequate wound healing. Prophylactic antibiotic therapy with third generation cephalosporin was applied. The child was discharged 10 days alter the surgery without associated neurosurgical complications (AU).
Assuntos
Humanos , Masculino , Recém-Nascido , Recém-Nascido/fisiologia , Meningomielocele/cirurgia , Meningomielocele/complicações , Meningomielocele/diagnóstico , Meningomielocele/epidemiologia , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Malformações Vasculares do Sistema Nervoso Central/mortalidade , Malformações Vasculares do Sistema Nervoso Central/terapia , Tubo Neural/anormalidades , Medula Espinal/anormalidades , Ácido Fólico/genéticaRESUMO
El Sistema Ventricular Cerebral se desarrolla de forma paralela al resto del Sistema Nervioso Central, facilitando la circulación del Líquido Cefalorraquídeo, desde su separación del líquido amniótico a nivel embrionario. Este desarrollo es necesario para entender correctamente la anatomía ventricular y facilitar el abordaje para patologías intraventriculares. El objetivo de esta revisión es reconocer los puntos más importantes en la embriología ventricular para facilitar el aprendizaje de la anatomía quirúrgica ventricular.
The cerebral ventricular system is developed in parallel with the rest of the central nervous system, facilitating the circulation of cerebrospinal fluid, from the amniotic fluid separation in the embryonic phases. This development is necessary to correctly understand the ventricular anatomy and facilitate approach to intraventricular pathologies. The objective of this review is to recognize the most important points in the ventricular embryology and in the intraventricular endoscopic vision to facilitate learning of the ventricular surgical anatomy.
Assuntos
Humanos , Endoscopia/métodos , Ventrículos Cerebrais/embriologia , Ventriculostomia/métodos , Sistema Nervoso Central , Tubo NeuralRESUMO
Heterotrimeric G protein signaling plays major roles during different cellular events. However, there is a limited understanding of the molecular mechanisms underlying G protein control during embryogenesis. G proteins are highly conserved and can be grouped into four subfamilies according to sequence homology and function. To further studies on G protein function during embryogenesis, the present analysis identified four Gα subunits representative of the different subfamilies and determined their spatiotemporal expression patterns during Xenopus tropicalis embryogenesis. Each of the Gα subunit transcripts was maternally and zygotically expressed, and, as development progressed, dynamic expression patterns were observed. In the early developmental stages, the Gα subunits were expressed in the animal hemisphere and dorsal marginal zone. While expression was observed at the somite boundaries, in vascular structures, in the eye, and in the otic vesicle during the later stages, expression was mainly found in neural tissues, such as the neural tube and, especially, in the cephalic vesicles, neural crest region, and neural crest-derived structures. Together, these results support the pleiotropism and complexity of G protein subfamily functions in different cellular events. The present study constitutes the most comprehensive description to date of the spatiotemporal expression patterns of Gα subunits during vertebrate development.
Assuntos
Diferenciação Celular/genética , Desenvolvimento Embrionário/genética , Proteínas Heterotriméricas de Ligação ao GTP/biossíntese , Xenopus/genética , Sequência de Aminoácidos/genética , Animais , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Heterotriméricas de Ligação ao GTP/genética , Hibridização In Situ , Crista Neural/crescimento & desenvolvimento , Crista Neural/metabolismo , Tubo Neural/crescimento & desenvolvimento , Tubo Neural/metabolismo , Transdução de Sinais , Somitos/crescimento & desenvolvimento , Somitos/metabolismo , Xenopus/crescimento & desenvolvimentoRESUMO
Sonic hedgehog (SHH) es un morfógeno esencial para el desarrollo del tubo neural, miembros y somitos. Variaciones en su expresión pueden ocasionar alteraciones en el sistema nervioso. Esto lo producen teratógenos, como el ácido valproico (VPA), el cual aumenta las especies reactivas de oxígeno, pudiendo contrarrestarse con la administración de vitamina E (VE). Se buscó determinar la expresión de SHH en tubo neural y médula espinal en embriones y fetos de ratones expuestos a VPA, VPA + VE y VE. Se conformaron 8 grupos de ratones hembra (Mus musculus). A los 8 días post-coito (p.c.) se les administró a los grupos 1 y 5 suero fisiológico 0,3 ml; grupos 2 y 6 VPA 600 mg/kg; grupos 3 y 7 VPA 600 mg/kg + VE 200 UI/kg; grupos 4 y 8 VE 200 UI/kg, todos los tratamientos vía oral. A los 12 días p.c., se sacrificaron los grupos 1, 2, 3 y 4, y a los 17 días los restantes. Fueron fijados en solución Bouin e incluidos en paraplast. Se realizaron cortes transversales a nivel torácico. Se utilizó anticuerpo policlonal anti-SHH (Santa Cruz, H-160, conejo), dilución 1:100. Se describió la morfología de las muestras marcadas positivamente, se midió la densidad óptica integrada y porcentaje de área inmunoreactiva. La expresión de SHH fue inmunopositiva en notocorda y placa del piso del tubo neural solo en embriones de 12 días p.c. Los grupos tratados con VPA+VE y VE presentaron mayor intensidad inmunohistoquímica y porcentaje de área inmunoreactiva en comparación al grupo tratado con VPA (p 0,0001) en la placa del piso, siendo similar al grupo control. En la notocorda, la intensidad de inmunoreacción fue similar a lo demostrado en la placa del piso, con diferencias significativas (p 0,0001), pero el porcentaje de área no arrojó diferencias. Los grupos de 17 días de gestación resultaron negativos a la expresión de SHH. La vitamina E regula la expresión de SHH en tubo neural, atenuando así los efectos del VPA.
Sonic hedgehog (SHH) is an essential morphogen for the development of neural tube, members and somites. Variations in expression can cause abnormalities in the nervous system. This will produce teratogens, such as valproic acid (VPA), which increases the reactive oxygen species and can be counteracted with the administration of vitamin E (VE). We sought to determine the expression of SHH in the neural tube and spinal cord in mice embryos and fetuses exposed to VPA, VPA + VE and VE. For the study we used 8 groups of female mice (Mus musculus). At day 8 post-coitus (p.c.) the groups were administered as follows: groups 1 and 5,0.3ml saline; groups 2 and 6, VPA 600 mg/kg; groups 3 and 7, VPA 600 mg / kg + VE 200 IU/kg; groups 4 and 8, VE 200 IU/kg, all treatments were given orally. On the 12th day p.c., groups 1, 2, 3 and 4 were euthanized and the remaining groups at day 17. They were fixed in Bouin solution and included in paraplast; thoracic cross sections were performed, anti-SHH polyclonal antibody (Santa Cruz, H-160, rabbit) dilution 1:100 was used. We described morphology of the positively labeled samples and measured integrated optic density and percentage of immunoreactivearea.SHH expression was immunopositive in notochord and floor plate of the neural tube in embryos only 12 day p.c. In the groups treated with VPA + VE and VE immunohistochemistry showed greater intensity and percentage of immunoreactive area compared to those in the group treated with VPA (p0.0001) in the floor plate, being similar to the control group. In the notochord, immunoreaction intensity was similar to that shown in the floor plate, with significant differences (p 0.0001), but the percentage of area showed no differences. The groups at day 17 of gestation were negative for the expression of SHH. VE regulates expression of SHH in neural tube, thus attenuating the effects of VPA.
Assuntos
Animais , Feminino , Gravidez , Camundongos , Proteínas Hedgehog/efeitos dos fármacos , Tubo Neural/efeitos dos fármacos , Tubo Neural/metabolismo , Ácido Valproico/administração & dosagem , Vitamina E/administração & dosagem , Proteínas Hedgehog/efeitos dos fármacos , Imuno-Histoquímica , Fatores de TempoRESUMO
The etiology underlying neural tube defects (NTDs) is not fully understood and is believed to involve a complex milieu of genetic and environmental factors. The A1298C polymorphism in the methylenetetrahydropholate reductase gene (MTHFR) has been associated with mild risk for NTDs. In this study, the genotype distribution of the MTHFR gene A1298C polymorphism and the levels of serum homocysteine, vitamin B12, and folate were evaluated in 33 children with NTDs, their mothers, and 46 healthy controls. Genotyping of the A1298C polymorphism was performed by real-time polymerase chain reaction. The A and C allele frequencies in children with NTDs and their mothers were similar to controls (P = 0.160). The 1298AA and 1298CC genotype frequencies (P = 0.551 and 0.062, respectively) in children with NTDs and their mothers did not differ from controls. On the other hand, the 1298AC genotype frequencies in children with NTDs and their mothers were significantly different from controls (P = 0.025). The genotype frequency of 1298AC was lower in children with NTDs than in controls. There was no significant association between clinical distribution of NTDs and 1298AA/AC/CC genotypes (P > 0.05). Serum vitamin B12 levels were higher in children with NTDs than their mothers and controls (P = 0.001). There were no differences among serum homocysteine and folate levels in all groups (P = 0.494 and 0.141, respectively). Both genetic and nutritional factors are important in the etiology of NTDs. Thus, the A1298C polymorphism cannot be regarded as a major risk factor for NTDs.