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Preterm birth accounts for about 10% of births worldwide. Studying risk factors for perinatal brain damage is essential, as findings suggest that almost 20% of disabilities are linked to risks in the early stages of development. This research aimed to study longitudinal changes in intelligence from 6 to 8 years of age in a sample of 39 preterm children with a history of risk of brain damage and a control group of 35 children born at term. The Wechsler Intelligence Scale (WISC-IV) was used to measure cognitive ability at six, seven, and eight years old. The results showed that the preterm group obtained significantly lower scores than the control group. The working memory indicator significantly affected the interaction between age and prematurity. We consider it crucial to expand the knowledge we have about the neurocognitive development of premature infants, both in specific cognitive domains and in age ranges, so that the information obtained can help predict the probability of presenting cognitive alterations from early stages. This, therefore, helps in implementing intervention strategies and programs based on scientific evidence, and their design is complemented by clinical experience and empirical and theoretical knowledge of the different professionals involved in infant cognitive intervention.
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Some parasites are known to influence brain proteins or induce changes in the functioning of the nervous system. In this study, our objective is to demonstrate how the two-dimensional gel technique is valuable for detecting differences in protein expression and providing detailed information on changes in the brain proteome during a parasitic infection. Subsequently, we seek to understand how the parasitic infection affects the protein composition in the brain and how this may be related to changes in brain function. By analyzing de novo-expressed proteins at 2, 4, and 8 weeks post-infection compared to the brains of the control mice, we observed that proteins expressed at 2 weeks are primarily associated with neuroprotection or the initial response of the mouse brain to the infection. At 8 weeks, parasitic infection can induce oxidative stress in the brain, potentially activating signaling pathways related to the response to cellular damage. Proteins expressed at 8 weeks exhibit a pattern indicating that, as the host fails to balance the Neuro-Immuno-Endocrine network of the organism, the brain begins to undergo an apoptotic process and consequently experiences brain damage.
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Parasitos , Doenças Parasitárias , Taenia , Animais , Camundongos , Encéfalo , Camundongos Endogâmicos BALB CRESUMO
The congenital Zika syndrome (CZS) has been characterized as a set of several brain changes, such as reduced brain volume and subcortical calcifications, in addition to cognitive deficits. Microcephaly is one of the possible complications found in newborns exposed to Zika virus (ZIKV) during pregnancy, although it is an impacting clinical sign. This study aimed to investigate the consequences of a model of congenital ZIKV infection by evaluating the histopathology, blood-brain barrier, and neuroinflammation in pup rats 24 h after birth, and neurodevelopment of the offspring. Pregnant rats were inoculated subcutaneously with ZIKV-BR at the dose 1 × 107 plaque-forming unit (PFU mL-1) of ZIKV isolated in Brazil (ZIKV-BR) on gestational day 18 (G18). A set of pups, 24 h after birth, was euthanized. The brain was collected and later evaluated for the histopathology of brain structures through histological analysis. Additionally, analyses of the blood-brain barrier were conducted using western blotting, and neuroinflammation was assessed using ELISA. Another set of animals was evaluated on postnatal days 3, 6, 9, and 12 for neurodevelopment by observing the developmental milestones. Our results revealed hippocampal atrophy in ZIKV animals, in addition to changes in the blood-brain barrier structure and pro-inflammatory cytokines expression increase. Regarding neurodevelopment, a delay in important reflexes during the neonatal period in ZIKV animals was observed. These findings advance the understanding of the pathophysiology of CZS and contribute to enhancing the rat model of CZS.
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Microcefalia , Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Gravidez , Humanos , Feminino , Ratos , Animais , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico , Zika virus/fisiologia , Complicações Infecciosas na Gravidez/patologia , Barreira Hematoencefálica/patologia , Doenças Neuroinflamatórias , Microcefalia/etiologia , Microcefalia/patologia , Atrofia/patologia , Hipocampo/patologiaRESUMO
OBJECTIVE: To examine the relationship between perioperative brain injury and neurodevelopment during early childhood in patients with severe congenital heart disease (CHD). STUDY DESIGN: One hundred and seventy children with CHD and born at term who required cardiopulmonary bypass surgery in the first 6 weeks after birth were recruited from 3 European centers and underwent preoperative and postoperative brain MRIs. Uniform description of imaging findings was performed and an overall brain injury score was created, based on the sum of the worst preoperative or postoperative brain injury subscores. Motor and cognitive outcomes were assessed with the Bayley Scales of Infant and Toddler Development Third Edition at 12 to 30 months of age. The relationship between brain injury score and clinical outcome was assessed using multiple linear regression analysis, adjusting for CHD severity, length of hospital stay (LOS), socioeconomic status (SES), and age at follow-up. RESULTS: Neither the overall brain injury score nor any of the brain injury subscores correlated with motor or cognitive outcome. The number of preoperative white matter lesions was significantly associated with gross motor outcome after correction for multiple testing (P = .013, ß = -0.50). SES was independently associated with cognitive outcome (P < .001, ß = 0.26), and LOS with motor outcome (P < .001, ß = -0.35). CONCLUSION: Preoperative white matter lesions appear to be the most predictive MRI marker for adverse early childhood gross motor outcome in this large European cohort of infants with severe CHD. LOS as a marker of disease severity, and SES influence outcome and future intervention trials need to address these risk factors.
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Lesões Encefálicas , Cardiopatias Congênitas , Lactente , Humanos , Pré-Escolar , Encéfalo/patologia , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/complicações , Imageamento por Ressonância Magnética , Fatores de RiscoRESUMO
Chronic opioid intake leads to several brain changes involved in the development of dependence, whereby an early hedonistic effect (liking) extends to the need to self-administer the drug (wanting), the latter being mostly a prefrontal-striatal function. The development of animal models for voluntary oral opioid intake represents an important tool for identifying the cellular and molecular alterations induced by chronic opioid use. Studies mainly in humans have shown that polydrug use and drug dependence are shared across various substances. We hypothesize that an animal bred for its alcohol preference would develop opioid dependence and further that this would be associated with the overt cortical abnormalities clinically described for opioid addicts. We show that Wistar-derived outbred UChB rats selected for their high alcohol preference additionally develop: (i) a preference for oral ingestion of morphine over water, resulting in morphine intake of 15 mg/kg/day; (ii) marked opioid dependence, as evidenced by the generation of strong withdrawal signs upon naloxone administration; (iii) prefrontal cortex alterations known to be associated with the loss of control over drug intake, namely, demyelination, axonal degeneration, and a reduction in glutamate transporter GLT-1 levels; and (iv) glial striatal neuroinflammation and brain oxidative stress, as previously reported for chronic alcohol and chronic nicotine use. These findings underline the relevance of polydrug animal models and their potential in the study of the wide spectrum of brain alterations induced by chronic morphine intake. This study should be valuable for future evaluations of therapeutic approaches for this devastating condition.
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Dependência de Morfina , Transtornos Relacionados ao Uso de Substâncias , Humanos , Ratos , Animais , Morfina/efeitos adversos , Analgésicos Opioides/farmacologia , Ratos Wistar , Naloxona/farmacologia , Encéfalo , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Etanol/farmacologia , Antagonistas de Entorpecentes/farmacologiaRESUMO
Assessing the levels of oxidative stress markers and antioxidant enzymes in the brain is crucial in evaluating its antioxidant capacity and understanding the influence of various dietary patterns on brain well-being. This study aimed to investigate the antioxidant status and oxidative damage in the brain of bat species with different feeding habits to gain insights into their protective mechanisms against oxidative stress and their interspecific variation. The levels of oxidative damage markers and the activities of antioxidants were measured in the brain of four bat species with different feeding habits, namely insectivorous, frugivorous, nectarivorous, and hematophagous. Insectivorous bats showed higher levels of SOD and fumarase compared to the other groups, while hematophagous bats showed lower levels of these enzymes. On the other hand, the activities of glutathione peroxidase and glutathione S-transferase were higher in hematophagous bats and lower in insectivorous bats. The carbonyl groups and malondialdehyde levels were lower in frugivores, while they were similar in the other feeding guilds. Nitrite and nitrate levels were higher in the hematophagous group and relatively lower in all other groups. The GSSG/GSH ratio was higher in the hematophagous group and lower in frugivores. Overall, our results indicate that the levels of oxidative stress markers and the activities of antioxidant enzymes in the brain vary significantly among bat species with different feeding habitats. The findings suggest that the antioxidant status of the brain is influenced by diet and feeding habits.
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Antioxidantes , Quirópteros , Animais , Antioxidantes/metabolismo , Glutationa/metabolismo , Estresse Oxidativo , Encéfalo/metabolismoRESUMO
BACKGROUND: The acquired brain damage is a common neurological disorder. OBJECTIVE: Determine the probabilistic intersections of variables related to acquired brain damage from the determination of a priori and a posteriori probabilities. METHOD: Analytical retrospective study. A descriptive analysis was carried out, confidence intervals were calculated to obtain the mean and the proportion with α = 0.05 considering the age of the patient and the diagnosis. An analysis of probabilistic intersection, a priori and a posteriori probability was performed considering diagnosis, sex and age decade; finally, chi squared was calculated. RESULTS: 736 patients were analyzed. The most frequent diagnosis was language disorder. The patients diagnosed with memory disorder were the youngest and those diagnosed with degenerative cognitive disorder the oldest. The probability that a patient with sequelae due to acquired brain damage arrives at the hospital, at the language pathology service, to be diagnosed with a language disorder and that this patient is also a man is 29.06%. CONCLUSIONS: The high prevalence of short and long-term disability generated by acquired brain damage highlights the importance of an early and timely detection and diagnosis so that it favors prompt and efficient specialized care.
ANTECEDENTES: El daño cerebral adquirido es un trastorno neurológico común. OBJETIVO: Determinar las intersecciones probabilísticas de variables relacionadas con daño cerebral adquirido a partir de la determinación de probabilidades a priori y a posteriori. MÉTODO: Estudio retrospectivo analítico. Se realizó análisis descriptivo y se calcularon intervalos de confianza para la media y para la proporción con α = 0.05 considerando la edad del paciente y el diagnóstico. Se realizó análisis de intersección probabilística, probabilidad a priori y a posteriori considerando el diagnóstico, el sexo y la década de edad; por último, se utilizó la prueba χ2. RESULTADOS: Se analizaron 736 pacientes. El diagnóstico más frecuente fue el trastorno del lenguaje. Los pacientes diagnosticados con trastorno de memoria fueron los más jóvenes y los diagnosticados con trastorno cognitivo degenerativo los más longevos. La probabilidad de que llegue al hospital, al servicio de patología de lenguaje, un paciente con secuelas por daño cerebral adquirido, sea diagnosticado con trastorno del lenguaje y sea hombre es del 29.06%. CONCLUSIONES: La alta prevalencia de discapacidad a corto y largo plazo generada por el daño cerebral adquirido indica la importancia de la detección y el diagnóstico temprano y oportuno que favorezcan una pronta y eficiente atención especializada.
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Lesões Encefálicas , Transtornos Cognitivos , Transtornos da Linguagem , Masculino , Humanos , Estudos Retrospectivos , Lesões Encefálicas/etiologia , Progressão da Doença , Transtornos da Linguagem/etiologiaRESUMO
Cerebral palsy (CP) is a neurodevelopmental disorder caused by damage to the immature brain. CP is considered the main cause of physical disability in childhood. Studies have shown that memory function and emotional behaviour are significantly impaired in CP. Current thought is that interventions for neuromotor damaged play a prominent role, but neglects the memory acquisition problems that affect the functioning and quality of life of these children. This systematic review aims to map and analyse pre-clinical interventions used to treat memory formation problems resulting from CP. For this, a search was carried out in the Pubmed, Web of Science, Scopus and Lilacs databases. Then, eligibility, extraction date and evaluation of the methodological quality of the studies were determined. 52 studies were included in this review, and 27 were included in a meta-analysis. Assessing memory performance as a primary outcome, and structural and biochemical changes in the hippocampus as a secondary outcome. CP models were reported to be induced by hypoxia-ischemia, oxygen deprivation and liposaccharide (LPS) exposure, resulting in impairments in the formation of short-term and long-term memory in adult life. A reduction in escape latency and dwell time were observed in the target quadrant as well as an increase in the time needed for the rodents to find the platform in the Morris Water Maze (MWM). Brain injuries during the perinatal period are considered an insult that negatively impacts hippocampus maturation and causes impairment in memory formation in adult life. Some studies reported that regions of the hippocampus such as the dentate gyrus and cornu ammonis 1 were impaired in CP, noting an increase in oxidative stress enzymes and pro-inflammatory cytokines, associated with a reduction in BDNF and neurogenesis levels. These were reported to cause a reduction in the number of neurons and the volume of the hippocampus, in addition to an increase in astrogliosis and apoptosis of neurons and difficulties in forming new memories similar to those that occur in children with CP. Interventions that reduced neuroinflammation and the presence of free radicals were highlighted as a therapy for the memory disturbance present in CP. Preclinical studies registered treatments with oxygen interventions, resveratrol and erythropoietin, which were able to reduce the damage to the hippocampus and promote improvements in memory and behaviour. In the meta-analysis of selected studies, we observed favorable results, through effect size, for the use of oxygen interventions (SDM -6.83 95% CI [-7.91, -5.75], Z = 12.38, p = 0.03; I2 = 71%), erythropoietin (SDM -3.16 95% CI [-4.27, -2.05], Z = 5.58, p = 0.002; I2 = 82%) and resveratrol (SDM -2.42 95% CI [-3.19, - 1.66], Z = 6.21, p = 0.01; I2 = 77%), stimulating plastic responses in the hippocampus and facilitating the memory formation, with these presenting positive effects in general (SDM -2.84 95% CI [-3.10, -2.59], Z = 22.00; p < 0.00001; I2 = 92.9%). These studies demonstrate possible avenues of intervention for memory alterations in experimental models of early brain injuries, highlighting promising interventions that can facilitate the maturation of the hippocampus and memory formation and, consequently, minimize functional problems that arise during development.
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Lesões Encefálicas , Paralisia Cerebral , Eritropoetina , Humanos , Paralisia Cerebral/complicações , Paralisia Cerebral/terapia , Qualidade de Vida , Resveratrol , Hipocampo , Transtornos da Memória/etiologia , Transtornos da Memória/terapia , Lesões Encefálicas/complicações , Lesões Encefálicas/terapiaRESUMO
Microglia, the resident macrophages of the central nervous system, are essential players during physiological and pathological processes. Although they participate in synaptic pruning and maintenance of neuronal circuits, microglia are mainly studied by their activity modulating inflammatory environment and adapting their phenotype and mechanisms to insults detected in the brain parenchyma. Changes in microglial phenotypes are reflected in their morphology, membrane markers, and secreted substances, stimulating neighbor glia and leading their responses to control stimuli. Understanding how microglia react in various microenvironments, such as chronic inflammation, made it possible to establish therapeutic windows and identify synergic interactions with acute damage events like stroke. Obesity is a low-grade chronic inflammatory state that gradually affects the central nervous system, promoting neuroinflammation development. Obese patients have the worst prognosis when they suffer a cerebral infarction due to basal neuroinflammation, then obesity-induced neuroinflammation could promote the priming of microglial cells and favor its neurotoxic response, potentially worsening patients' prognosis. This review discusses the main microglia findings in the obesity context during the course and resolution of cerebral infarction, involving the temporality of the phenotype changes and balance of pro- and anti-inflammatory responses, which is lost in the swollen brain of an obese subject. Obesity enhances proinflammatory responses during a stroke. Obesity-induced systemic inflammation promotes microglial M1 polarization and priming, which enhances stroke-associated damage, increasing M1 and decreasing M2 responses.
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Microglia , Acidente Vascular Cerebral , Humanos , Microglia/patologia , Doenças Neuroinflamatórias , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Inflamação/patologia , Infarto Cerebral/patologia , Obesidade/complicaçõesRESUMO
BACKGROUND: Helicobacter pylori (Hp) infects the stomach of 50% of the world's population. Importantly, chronic infection by this bacterium correlates with the appearance of several extra-gastric pathologies, including neurodegenerative diseases. In such conditions, brain astrocytes become reactive and neurotoxic. However, it is still unclear whether this highly prevalent bacterium or the nanosized outer membrane vesicles (OMVs) they produce, can reach the brain, thus affecting neurons/astrocytes. Here, we evaluated the effects of Hp OMVs on astrocytes and neurons in vivo and in vitro. METHODS: Purified OMVs were characterized by mass spectrometry (MS/MS). Labeled OMVs were administered orally or injected into the mouse tail vein to study OMV-brain distribution. By immunofluorescence of tissue samples, we evaluated: GFAP (astrocytes), ßIII tubulin (neurons), and urease (OMVs). The in vitro effect of OMVs in astrocytes was assessed by monitoring NF-κB activation, expression of reactivity markers, cytokines in astrocyte-conditioned medium (ACM), and neuronal cell viability. RESULTS: Urease and GroEL were prominent proteins in OMVs. Urease (OMVs) was present in the mouse brain and its detection coincided with astrocyte reactivity and neuronal damage. In vitro, OMVs induced astrocyte reactivity by increasing the intermediate filament proteins GFAP and vimentin, the plasma membrane αVß3 integrin, and the hemichannel connexin 43. OMVs also produced neurotoxic factors and promoted the release of IFNγ in a manner dependent on the activation of the transcription factor NF-κB. Surface antigens on reactive astrocytes, as well as secreted factors in response to OMVs, were shown to inhibit neurite outgrowth and damage neurons. CONCLUSIONS: OMVs administered orally or injected into the mouse bloodstream reach the brain, altering astrocyte function and promoting neuronal damage in vivo. The effects of OMVs on astrocytes were confirmed in vitro and shown to be NF-κB-dependent. These findings suggest that Hp could trigger systemic effects by releasing nanosized vesicles that cross epithelial barriers and access the CNS, thus altering brain cells.
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Helicobacter pylori , Camundongos , Animais , Helicobacter pylori/metabolismo , Astrócitos , Urease/metabolismo , Urease/farmacologia , NF-kappa B/metabolismo , Fator B do Complemento/metabolismo , Fator B do Complemento/farmacologia , Modelos Animais de Doenças , Espectrometria de Massas em Tandem , NeurôniosRESUMO
BACKGROUND: In response to brain injury or inflammation, astrocytes undergo hypertrophy, proliferate, and migrate to the damaged zone. These changes, collectively known as "astrogliosis", initially protect the brain; however, astrogliosis can also cause neuronal dysfunction. Additionally, these astrocytes undergo intracellular changes involving alterations in the expression and localization of many proteins, including αvß3 integrin. Our previous reports indicate that Thy-1, a neuronal glycoprotein, binds to this integrin inducing Connexin43 (Cx43) hemichannel (HC) opening, ATP release, and astrocyte migration. Despite such insight, important links and molecular events leading to astrogliosis remain to be defined. METHODS: Using bioinformatics approaches, we analyzed different Gene Expression Omnibus datasets to identify changes occurring in reactive astrocytes as compared to astrocytes from the normal mouse brain. In silico analysis was validated by both qRT-PCR and immunoblotting using reactive astrocyte cultures from the normal rat brain treated with TNF and from the brain of a hSOD1G93A transgenic mouse model. We evaluated the phosphorylation of Cx43 serine residue 373 (S373) by AKT and ATP release as a functional assay for HC opening. In vivo experiments were also performed with an AKT inhibitor (AKTi). RESULTS: The bioinformatics analysis revealed that genes of the PI3K/AKT signaling pathway were among the most significantly altered in reactive astrocytes. mRNA and protein levels of PI3K, AKT, as well as Cx43, were elevated in reactive astrocytes from normal rats and from hSOD1G93A transgenic mice, as compared to controls. In vitro, reactive astrocytes stimulated with Thy-1 responded by activating AKT, which phosphorylated S373Cx43. Increased pS373Cx43 augmented the release of ATP to the extracellular medium and AKTi inhibited these Thy-1-induced responses. Furthermore, in an in vivo model of inflammation (brain damage), AKTi decreased the levels of astrocyte reactivity markers and S373Cx43 phosphorylation. CONCLUSIONS: Here, we identify changes in the PI3K/AKT molecular signaling network and show how they participate in astrogliosis by regulating the HC protein Cx43. Moreover, because HC opening and ATP release are important in astrocyte reactivity, the phosphorylation of Cx43 by AKT and the associated increase in ATP release identify a potential therapeutic window of opportunity to limit the adverse effects of astrogliosis.
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Lesões Encefálicas , Conexina 43 , Animais , Camundongos , Ratos , Trifosfato de Adenosina/farmacologia , Trifosfato de Adenosina/metabolismo , Astrócitos/metabolismo , Lesões Encefálicas/metabolismo , Conexina 43/metabolismo , Gliose/metabolismo , Inflamação/metabolismo , Integrina beta3/genética , Integrina beta3/metabolismo , Integrina beta3/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para Cima , Antígenos Thy-1/metabolismo , Integrina alfa5/metabolismoRESUMO
This opinion paper presents a brief review on the potential use of Creatine (Cr) to improve the inflammatory profile in individuals with Cerebral Palsy (CP). CP is a condition that causes muscle atrophy followed by reduced strength and altered muscle tone. The prevalence of chronic diseases is higher in people with CP due to this, which are often associated with peripheral inflammation, but there are no studies that have evaluated central inflammation in this condition. Nevertheless, the anti-inflammatory action of Cr has already been observed in different types of studies. Thus, the use of experimental models of CP to evaluate the expression of the inflammatory markers, especially in the brain, as well as approaches to reduce the impairments already observed becomes essential. Results obtained in these preclinical studies may contribute to the quality of therapeutic strategies offered to children suffering from CP, the most common cause of chronic motor disability in childhood.
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Paralisia Cerebral , Pessoas com Deficiência , Transtornos Motores , Criança , Humanos , Paralisia Cerebral/complicações , Creatina/uso terapêutico , Transtornos Motores/complicações , Inflamação/tratamento farmacológico , Inflamação/complicações , Suplementos NutricionaisRESUMO
RESUMEN El objetivo del estudio estuvo dirigido a establecer los indicadores de alteraciones psicosociales y las dimensiones que interfieren en la calidad de vida, según el paciente con daño cerebral adquirido, sus familiares y los especialistas de asistencia, pertenecientes al Consejo Popular San Juan de Dios. Se realizó un estudio mixto cuanticualitativo en el período comprendido entre mayo de 2018 y mayo de 2020, el que se extiende hasta hoy, atendiendo a los resultados que se han incorporado a la práctica médica sobre la base de la implementación de un proyecto de investigación que se ejecutó a partir de la colaboración entre el Centro de Desarrollo de las Ciencias Sociales y Humanísticas en Salud y el Hospital Universitario Manuel Ascunce Domenech, de Camagüey. La muestra la constituyeron 30 pacientes y sus familiares, pertenecientes a los consultorios de mayor prevalencia en los casos objeto de estudio. Para el desarrollo de la investigación se emplearon métodos empíricos, teóricos y matemático-estadísticos y se aplicó la escala de la calidad de vida del paciente con daño cerebral (CAVIDACE), dirigida a la familia. Como principales resultados se determinó que las principales funciones psíquicas superiores que mostraron alteraciones fueron los procesos de atención y memoria. Se apreciaron en la mayoría de los pacientes alteraciones emocionales, conductuales, en la autonomía funcional y en la integración social. Las dimensiones de la calidad de vida que evidencian más alteraciones fueron la inserción social, el bienestar emocional y físico, el desarrollo personal y las relaciones interpersonales. De acuerdo con el percentil de la escala se evidenciaron resultados de calidad de vida baja en la mayoría de los pacientes, posterior al daño cerebral adquirido.
ABSTRACT The general objective of the study was aimed at establishing the indicators of psychosocial alterations and the dimensions that interfere with quality of life, according to the patient with acquired brain injury, their relatives and assistance specialists, belonging to the San Juan de Dios Popular Council. A mixed quantitative-qualitative study was carried out in the period between May 2018 and May 2020, which extends until today, based on the results that have been incorporated into medical practice based on the implementation of a research project that It was executed from the collaboration between the Center for the Development of Social and Humanistic Sciences in Health and the Manuel Ascunce Domenech University Hospital, in Camagüey. The sample was made up of 30 patients and their relatives, belonging to the most prevalent clinics in the cases under study. For the development of the research, empirical, theoretical and mathematical-statistical methods were used, and the scale of the quality of life of the patient with brain damage (CAVIDACE), aimed at the family, was applied. As main results, it was determined that the main superior psychic functions that showed alterations were: attention and memory processes. Emotional, behavioral, functional autonomy and social integration alterations were observed in most of the patients. The dimensions of quality of life that showed more alterations were: social insertion, emotional and physical well-being, personal development and interpersonal relationships. According to the percentile of the scale, results of low quality of life were evidenced in most of the patients, after to the acquired cerebral damage.
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The objective was compare the morphological damages in brain and to evaluate the participation of oxidative stress, using two animal models of shaken baby syndrome (SBS). Five-day-old Wistar rats were used to develop two models of SBS as follows: Gyrotwister (GT) group was subjected to low intensity, high duration rotating movements and Ratshaker (RS) group made to undergo high intensity, low duration anteroposterior movements. Both groups presented respiratory distress, weight loss and shorter stature compared with the control group. In addition, involuntary movements occurred in both experimental models. Hemorrhage was observed in 10 % of the GT group and in 40 % of the RS group. This last group experienced lesser weight gain at 30 days. Glutathione decreased by 25.7 % (GT) and 59.96 (RT). Cell data analysis revealed the presence of crenate and pyknotic cells, characterized by apparent absence of nucleus and nucleolus as well as vacuolation in the GT group. In the RS group, there were a high number of angular, pyknotic and shrunken cells, and a lot of vacuolization. The severity of the brain damage can be related to the magnitude of biochemical modifications, specifically, those related to the production of reactive oxygen or nitrogen species, oxidative stress, oxidative damage.
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Síndrome do Bebê Sacudido , Animais , Encéfalo , Modelos Animais , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
BACKGROUND: Approximately 10% of adolescents worldwide are overweight or obese, hence the urgent and universal need to elucidate possible mechanisms that lead to obesity in the adolescent population. OBJECTIVES: We examined the hypothalamic metabolism and its relationship with physical development in obese and eutrophic adolescents. METHODS: We performed a case-control study with 115 adolescents between 11 and 18 years of age, to compare obese (BMI z-score ≥ 2) and nonobese individuals (eutrophic controls; BMI z-score ≤ 1). The following hypothalamic metabolite ratios were examined as primary outcomes: glutamate/creatine (Cr), the sum of glutamate and glutamine/Cr, N-acetylaspartate (NAA)/Cr, myoinositol/Cr, and total choline/Cr (glycerophosphocholine + phosphocholine/Cr), quantified by magnetic resonance spectroscopy. BMI z-scores, pubertal status, and scores on the Yale Food Addiction Scale, the Binge Eating Scale, and the Child Depression Inventory were assessed as secondary outcomes. Pearson coefficients (r) or nonparametric Spearman correlation (rho) analyses were performed between hypothalamic metabolite ratios and other parameters, such as BMI z-scores, physical development, food habits, depression symptoms, and serum protein concentrations (cytokines, hormones, and neuropeptides). RESULTS: Adolescents with obesity showed a lower hypothalamic NAA/Cr ratio (0.70 ± 0.19) compared to their eutrophic counterparts (0.84 ± 0.20; P = 0.004). The NAA/Cr ratio was negatively correlated with BMI z-scores (r = -0.25; P = 0.03) and serum insulin (rho = -0.27; P = 0.04), C-peptide (rho = -0.26; P = 0.04), amylin (r = -0.27; P = 0.04), ghrelin (rho = -0.30; P = 0.02), and neuropeptide Y (r = -0.27; P = 0.04). Also, the NAA/Cr ratio was positively correlated with circulating IL-8 levels (rho = 0.26; P = 0.04). CONCLUSIONS: High BMI z-scores are associated with lower hypothalamic NAA/Cr ratios. The negative correlations found between the NAA/Cr ratio and serum cytokines, hormones, and neuropeptides suggest a broad cross-talk linking hormonal imbalances, neurohumoral alterations, and hypothalamic functions in adolescents with obesity.
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Creatina , Obesidade Infantil , Adolescente , Ácido Aspártico/análogos & derivados , Estudos de Casos e Controles , Criança , Colina/metabolismo , Creatina/metabolismo , Citocinas , Ácido Glutâmico/metabolismo , Hormônios , HumanosAssuntos
Encefalopatias , Polifenóis , Humanos , Polifenóis/uso terapêutico , Flavonoides , AntioxidantesRESUMO
Ethylmalonic encephalopathy (EE) is a severe intoxication disorder caused by mutations in the ETHE1 gene that encodes a mitochondrial sulfur dioxygenase involved in the catabolism of hydrogen sulfide. It is biochemically characterized by tissue accumulation of hydrogen sulfide and its by-product thiosulfate, as well as of ethylmalonic acid due to hydrogen sulfide-induced inhibition of short-chain acyl-CoA dehydrogenase. Patients usually present with early onset severe brain damage associated to encephalopathy, chronic hemorrhagic diarrhea and vascular lesions with petechial purpura and orthostatic acrocyanosis whose pathophysiology is poorly known. Current treatment aims to reduce hydrogen sulfide accumulation, but does not significantly prevent encephalopathy and most fatalities. In this review, we will summarize the present knowledge obtained from human and animal studies showing that disruption of mitochondrial and redox homeostasis may represent relevant pathomechanisms of tissue damage in EE. Mounting evidence show that hydrogen sulfide and ethylmalonic acid markedly disturb critical mitochondrial functions and induce oxidative stress. Novel therapeutic strategies using promising candidate drugs for this devastating disease are also discussed.
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Lesões Encefálicas , Púrpura , Animais , Encéfalo/metabolismo , Encefalopatias Metabólicas Congênitas , Lesões Encefálicas/metabolismo , Homeostase , Humanos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas de Transporte Nucleocitoplasmático/genética , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Oxirredução , Púrpura/genética , Púrpura/metabolismo , Púrpura/patologiaRESUMO
Leigh syndrome is an inherited neurodegenerative disorder of infancy that typically manifests between 3 and 12 months of age. The common neurological manifestations are developmental delay or regression, progressive cognitive decline, dystonia, ataxia, brainstem dysfunction, epileptic seizures, and respiratory dysfunction. Although the disorder is clinically and genetically heterogeneous, the histopathological and radiological features characteristically show focal and bilaterally symmetrical, necrotic lesions in the basal ganglia and brainstem. The syndrome has a characteristic histopathological signature that helps in clinching the diagnosis. We discuss these unique findings on autopsy and radiology in a young infant who succumbed to a subacute, progressive neurological illness suggestive of Leigh syndrome. Our case highlights that Leigh syndrome should be considered in the differential diagnosis of infantile-onset, subacute neuroregression with dystonia and seizures, a high anion gap metabolic acidosis, normal ketones, elevated lactates in blood, brain, and urine, and bilateral basal ganglia involvement.
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BACKGROUND: Morphological alterations in intracranial pressure (ICP) pulse waveform (ICPW) secondary to intracranial hypertension (ICP >20 mmHg) and a reduction in intracranial compliance (ICC) are well known indicators of neurological severity. The exclusive exploration of modifications in ICPW after either the loss of skull integrity or surgical procedures for intracranial hypertension resolution is not a common approach studied. The present study aimed to assess the morphological alterations in ICPW among neurocritical care patients with skull defects and decompressive craniectomy (DC) by comparing the variations in ICPW features according to elevations in mean ICP values. METHODS: Patients requiring ICP monitoring because of acute brain injury were included. A continuous record of 10 min-length for the beat-by-beat analysis of ICPW was performed, with ICP elevation produced by means of ultrasound-guided manual internal jugular vein compression at the end of the record. ICPW features (peak amplitude ratio (P2/P1), time interval to pulse peak (TTP) and pulse amplitude) were counterweighed between baseline and compression periods. Results were distributed for three groups: intact skull (exclusive burr hole for ICP monitoring), craniotomy/large fractures (group 2) or DC (group 3). RESULTS: 57 patients were analyzed. A total of 21 (36%) presented no skull defects, 21 (36%) belonged to group 2, whereas 15 (26%) had DC. ICP was not significantly different between groups: ±15.11 for intact, 15.33 for group 2 and ±20.81 mmHg for group 3, with ICP-induced elevation also similar between groups (p = 0.56). Significant elevation was observed for the P2/P1 ratio for groups 1 and 2, whereas a reduction was observed in group 3 (elevation of ±0.09 for groups 1 and 2, but a reduction of 0.03 for group 3, p = 0.01), and no significant results were obtained for TTP and pulse amplitudes. CONCLUSION: In the present study, intracranial pressure pulse waveform analysis indicated that intracranial compliance was significantly more impaired among decompressive craniectomy patients, although ICPW indicated DC to be protective for further influences of ICP elevations over the brain. The analysis of ICPW seems to be an alternative to real-time ICC assessment.
RESUMO
D-2-hydroxyglutaric acid (D-2-HG) accumulates and is the biochemical hallmark of D-2-hydroxyglutaric acidurias (D-2-HGA) types I and II, which comprehend two inherited neurometabolic diseases with severe cerebral abnormalities. Since the pathogenesis of these diseases is poorly established, we tested whether D-2-HG could be neurotoxic to neonatal rats. D-2-HG intracerebroventricular administration caused marked vacuolation in cerebral cortex and striatum. In addition, glial fibrillary acidic protein (GFAP), S-100 calcium binding protein B (S100B) and ionized calcium-binding adapter molecule 1 (Iba-1) staining was increased in both brain structures, suggesting glial reactivity and microglial activation. D-2-HG also provoked a reduction of NeuN-positive cells in cerebral cortex, signaling neuronal death. Considering that disturbances in redox homeostasis and energy metabolism may be involved in neuronal damage and glial reactivity, we assessed whether D-2-HG could induce oxidative stress and bioenergetics impairment. D-2-HG treatment significantly augmented reactive oxygen and nitrogen species generation, provoked lipid peroxidation and protein oxidative damage, diminished glutathione concentrations and augmented superoxide dismutase and catalase activities in cerebral cortex. Increased reactive oxygen species generation, lipoperoxidation and protein oxidation were also found in striatum. Furthermore, the antagonist of NMDA glutamate receptor MK-801 and the antioxidant melatonin were able to prevent most of D-2-HG-induced pro-oxidant effects, implying the participation of these receptors in D-2-HG-elicited oxidative damage. Our results also demonstrated that D-2-HG markedly reduced the respiratory chain complex IV and creatine kinase activities. It is presumed that these deleterious pathomechanisms caused by D-2-HGA may be involved in the brain abnormalities characteristic of early-infantile onset D-2-HGA.