Listeria monocytogenesy mecanismo de caballo de Troya a través de la barrera hematoencefálica / isteria monocytogenesand Trojan horse mechanism across the blood-brain barrier

Las infecciones del sistema nervioso central son potencialmente mortales, causadas por patógenos, como bacterias, virus y hongos. Para llegar hasta el cerebro, los microorganismos utilizan diversas vías y formas. Este patogeno es una bacteria grampositiva corta, flagelar e intracelular, con la capacidad de inducir su internalización en células fagocíticas (monocitos/macrófagos) y no fagocíticas (células endoteliales). Al infectar los macrófagos, estos microorganismos se valen de su capacidad de fijación, adhesión y migración transendotelial, para cruzar la barrera hematoencefálica, finalmente, generando meningitis bacteriana. En esta revisión describimos el mecanismo de caballo de Troya usado por Listeria monocytogenespara invadir el cerebro en el desarrollo de enfermedades infecciosas e incorporamos nuevos conocimientos sobre moléculas que intervienen en dicho mecanismo(AU)

Central nervous system infections are life-threatening, caused by pathogens such as bacteria, viruses and fungi. To access the brain, microorganisms use various mechanisms. Listeria monocytogenes is a short, flagellar and intracellular gram-positive bacterium, with the ability to induce its internalization in phagocytic (monocytes/macrophages) and non-phagocytic (endothelial cells) cells. By infecting macrophages, these microorganisms take advantage of their binding, adhesion, and transendothelial migrationcapacity to cross the blood-brain barrier, finally generating bacterial meningitis. In this review we describe the Trojan horse mechanism used by Listeria monocytogenesto invade the brain in the development of infectious diseases and we incorporate new knowledge about molecules that intervene in this mechanism(AU)

Diferencias cliniconeurológicas en pacientes con enfermedad cerebrovascular isquémica de edades menores y mayores de 65 años

Introducción: La enfermedad cerebrovascular isquémica tiene una alta frecuencia debida, fundamentalmente, al envejecimiento poblacional. Objetivo: Comparar las características clínicas de pacientes con enfermedad cerebrovascular isquémica de dos grupos etarios. Métodos: Se realizó un estudio descriptivo, transversal y retrospectivo en 36 pacientes con enfermedad cerebrovascular isquémica correspondientes a dos grupos etarios (65 y menos años y mayores de 65), quienes fueron atendidos en el Instituto de Neurología y Neurocirugía, La Habana, de enero a diciembre del 2017. Al respecto, se analizaron variables demográficas y clínicas y se aplicaron diferentes pruebas estadísticas para comparar. Resultados: Se obtuvo un aumento significativo de pacientes hipertensos (88,9 %) en el grupo etario mayor de 65 años. La mediana de la escala de ictus del National Institute of Health fue superior en estos pacientes (mediana [10-90 percentil]: 9,5 (4-19]). Hubo incremento estadístico de los mayores de 65 años con parálisis parcial de la mirada y ataxia; en tanto, la monoparesia y la extinción visual predominaron en los de 65 y menos años. Dicha escala mostró un aumento estadístico en el ictus aterotrombótico y cardioembólico en comparación con otras causas en ambos grupos. Los pacientes mayores de 65 años con solo un factor de riesgo o ninguno y los que eran hipertensos tuvieron mayor puntuación de la escala. Conclusiones: El grado de afectación neurológica fue superior en los mayores de 65 años que tenían un factor de riesgo y en aquellos con hipertensión arterial. Puede sugerirse que los mecanismos moleculares y fisiopatológicos de estos pacientes varían según la edad.

Introduction: The ischemic cerebrovascular disease has a high frequency due to the population aging mainly. Objective: To compare clinical characteristics of patients with ischemic cerebrovascular of two age groups. Methods: A descriptive, cross-sectional, retrospective study was carried out in the Neurology and Neurosurgery Institute in Havana, from January to December, 2017 in patients with ischemic cerebrovascular disease; 36 individuals of both age groups. In this regard, demographic variables, risk factors, clinical manifestations, coma scale and neurological deficiency, etiology and localization of the ischemic ictus were analyzed. Results: The 65 years group had a significant increase of hypertensive patients (88.9%). The average of the National Institute of Health stroke scale was superior in these patients (median [10-90 percentile]: 9.5 [4-19]). There was statistical increment of over 65 years patients with partial paralysis of the look and ataxia, but monoparesis and visual extinction in the age under 65 years. Such a scale had a statistical increase in the atherothrombotic and cardioembolic ictus in comparison with other etiologies in both patient groups. The over 65 years patients with just one risk factor or and those with hypertension had a higher punctuation of the scale. Conclusions: The degree of neurological affectation was higher in over 65 years patients that had a risk factor and in those with hypertension. As a result it could be suggested that the molecular and pathophysiolologic mechanisms of these patients vary with the age.

Craniectomía descompresiva en infarto de arteria cerebral media bilateral asociado a COVID-19. Reporte de caso / Decompressive Craniectomy in Bilateral Middle Cerebral Artery Infarction Associated with COVID-19: A Case Report

Resumen El nuevo síndrome respiratorio agudo severo por coronavirus tipo 2 (SARS-CoV-2) que causa la enfermedad por COVID-19, se detectó por primera vez en diciembre de 2019. En donde se ha visto que existe un estado protrombótico con afección al sistema nervioso central, con afectación a vasos de gran calibre como la arteria cerebral media, se debe a mecanismos inducidos por la propia infección, estado de hipercoagulabilidad y daño endotelial. Las manifestaciones neurológicas en el COVID-19 se encuentran en el 36% de los pacientes. Descripción del caso: Se trata de un paciente del sexo masculino, de 36 años de edad, con fiebre, tos y malestar general, a quien se le realizó una prueba COVID que resultó positiva, con empeoramiento del cuadro al que se agregó fotofobia, hemiparesia derecha y desviación de la comisura labial hacia la izquierda, por lo que fue llevado a un facultativo 8 horas después del inicio del cuadro clínico. Ahí se realizó una tomografía de cráneo simple que evidenció infarto extenso de la arteria cerebral media izquierda, con edema cerebral maligno, el cual se derivó a manejo quirúrgico de urgencia donde se le realizó una craniectomía descompresiva izquierda extensa. Después de esto, se mantuvo con asistencia respiratoria por intubación mecánica y medidas antiedema cerebral, y se logró que hubiera progresión ventilatoria; sin embargo, se le realizó traqueostomía y gastrostomía por presentar malos predictores de extubación. Se mantuvo en observación posquirúrgica y quedó con hemiparesia 3/5 derecha, sin algún otro déficit, por lo que se dio egreso a domicilio. Discusión: El caso presentado fue manejado con craniectomía descompresiva extensa, y se obtuvo mejoría en la supervivencia y pronóstico funcional, al igual que lo reportado en la literatura médica, en donde se recomienda que dicho manejo se realice de forma temprana. Conclusiones: El presente informe nos revela que aquellos pacientes hombres jóvenes en la cuarta y quinta década de la vida, con COVID-19 e infarto de arteria cerebral media, se presentan sin comorbilidades al darse tratamiento temprano con hemicraniectomía descompresiva, el cual mejora su pronóstico de vida, concordando con los casos presentados en la literatura médica.

Abstract The new severe acute respiratory syndrome due to coronavirus type 2 (SARS-CoV-2), which causes COVID-19 disease, was detected for the first time in December 2019. Where it has been seen that there is a prothrombotic state with involvement of the Central Nervous, with involvement of large vessels such as the middle cerebral artery, is due to mechanisms induced by the infection itself, hypercoagulable state and endothelial damage. Neurological manifestations in COVID-19 are found in 36% of patients. Case description: This is a 36-year-old male patient with fever, cough and general malaise. A COVID test was performed, which came out positive. His condition was getting worse adding photophobia, right hemiparesis and deviation of the corner of the mouth to the left, which is why he went to the doctor, arriving 8 hours after the onset of the clinical picture, where a simple skull tomography was performed, showing extensive infarction of the left middle cerebral artery with malignant cerebral edema. He was transferred to emergency surgical management where a left decompressive craniectomy was performed. After this, mechanical respiratory assistance with intubation and anti-cerebral edema measures were maintained, achieving ventilatory progression; however, a tracheostomy and gastrostomy were performed due to poor predictors of extubation. He was kept under post-surgical observation, leaving him with 3/5 right hemiparesis, without any other deficit, therefore, he was discharged home. Discussion: The case presented was managed with decompressive craniectomy, resulting in an improvement in survival, as reported in the literature where it is recommended that such management should be performed early. Conclusions: This report reveals that patients with COVID-19 present in young men in the fourth and fifth decade of life, without comorbidities, that recieved early treatment with decompressive hemicraniectomy, improved their life prognosis, consistent with the cases presented in the literature.

Escenarios para el diagnóstico de encefalopatía hipóxico isquémica e inicio de tratamiento con hipotermia controlada en recién nacidos con asfixia perinatal

La hipoxia isquemia perinatal y su complicación más temida, la encefalopatía hipóxica isquémica, continúa siendo uno de los principales motivos de ingreso a las unidades de cuidados neonatales. En la actualidad la hipotermia controlada es el tratamiento recomendado para los pacientes con encefalopatía moderada a severa, dado su carácter de neuroprotección ante la injuria cerebral hipóxico isquémica. Si bien los criterios de inclusión en esta terapia han sido bien establecidos, aún hay dificultades tanto en la identificación precoz de aquellos que pueden verse beneficiados, como en la toma de decisiones ante situaciones de controversia entre la evidencia disponible y la que se está gestando en estudios en curso. Este artículo pretende aportar herramientas al clínico para abordar diferentes escenarios que surgen de la práctica diaria.

Summary: Perinatal hypoxic ischemia and its most feared complication, hypoxic ischemic encephalopathy, remain one of the main reasons for admission to neonatal care. Controlled hypothermia is currently the recommended treatment for patients with moderate to severe encephalopathy, given its neuroprotective nature against hypoxic-ischemic brain injury. Although the inclusion criteria for this therapy have been well established, there are still difficulties both in the early identification of those who may benefit, and in making decisions regarding situations of controversy between the available evidence and that being developing in ongoing studies. This paper aims at providing tools so that clinicians can address different scenarios that arise during their daily practice.

A hipóxia isquêmica perinatal e sua complicação mais temida, a encefalopatia hipóxico-isquêmica, continuam sendo um dos principais motivos de internação em unidades de cuidados neonatais. A hipotermia controlada é atualmente o tratamento recomendado para pacientes com encefalopatia moderada a grave, dada a sua natureza neuroprotetora contra lesão cerebral hipóxico-isquêmica. Embora os critérios de inclusão dessa terapia estejam bem estabelecidos, ainda há dificuldades tanto na identificação precoce daqueles que podem se beneficiar, quanto na tomada de decisões em situações de controvérsia entre as evidências disponíveis e aquelas que estão se desenvolvendo em estudos em andamento. Este paper tem como objetivo fornecer ferramentas aos clínicos para abordar diferentes cenários que surgem da prática diária.

A systematic review and meta-analysis on abnormal posturing among brain injury patients / Uma revisão sistemática e metanálise sobre postura anormal entre pacientes com lesão cerebral

Abstract Background Abnormal motor posturing (AMP), exhibiting as decorticate, decerebrate, or opisthotonos, is regularly noticed among children and adults. Objective This systematic review and meta-analysis examined the risk factors and outcome of posturing among severe head and brain injury subjects. Methods Based on the inclusion and exclusion criteria and using MeSH terms: "decerebrate posturing", "opisthotonic posturing", "brain injury", and/or "cerebral injury" articles were searched on Scopus, PubMed, Science Direct, and google scholar databases. Observational studies, case series, and case reports were included. Results A total of 1953 studies were retrieved initially, and based on the selection criteria, 20 studies were finally selected for review and were analyzed for meta-analysis based on the mortality between the hematomas. The functional outcomes of this study are the risk factors, mortality rate and Glasgow Outcome Scale. Decerebrative patients were higher among the studies related to head injury surgeries. Males were mainly treated for decerebrate postures compared with the female subjects. Extradural hematoma and acute subdural hematoma with cerebral contusion were quite common in the surgical mass lesions. Conclusion The findings reported that the lesion types, the operative procedures, and the age of the decerebrating patients with brain injuries are the significant prognostic factors determining the survival outcomes.

Resumo Antecedentes Postura motora anormal (AMP), exibindo-se como decorticada, descerebrada ou opistótono, é regularmente observada entre crianças e adultos. Objetivo Esta revisão sistemática e metanálise examinou os fatores de risco e os resultados da postura entre indivíduos com lesões graves na cabeça e no cérebro. Métodos Com base nos critérios de inclusão e exclusão e usando termos MeSH: artigos sobre "postura descerebrada", "postura opistótona", "lesão cerebral" e/ou "lesão cerebral" foram pesquisados nas bases de dados Scopus, PubMed, Science Direct e Google Scholar. Foram incluídos estudos observacionais, séries de casos e relatos de casos. Resultados Um total de 1.953 estudos foram recuperados inicialmente e, com base nos critérios de seleção, 20 estudos foram finalmente selecionados para revisão e analisados para metanálise com base na mortalidade entre os hematomas. Os resultados funcionais deste estudo são os fatores de risco, taxa de mortalidade e Escala de Resultados de Glasgow. Os pacientes descerebrados foram maiores entre os estudos relacionados a cirurgias de traumatismo cranioencefálico. Os homens foram tratados principalmente para posturas descerebradas em comparação com as mulheres. Hematoma extradural e hematoma subdural agudo com contusão cerebral foram bastante comuns nas lesões de massa cirúrgica. Conclusão Os achados relataram que os tipos de lesões, os procedimentos operatórios e a idade dos pacientes descerebrados com lesões cerebrais são os fatores prognósticos significativos que determinam os resultados de sobrevivência.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 1 / Princípios da estimulação cerebral profunda na doença de Parkinson na prática clínica: parte 1

Abstract Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.

Resumo Nas últimas três décadas, a estimulação cerebral profunda (ECP) se tornou um tratamento bem estabelecido para doença de Parkinson (DP) e outros transtornos do movimento. A eficácia a longo prazo na DP foi bem documentada para a melhora dos sintomas motores cardinais da DP e das complicações induzidas pelo uso do levodopa, como as flutuações motoras e as discinesias. O momento da seleção do paciente é crucial para se obter os benefícios ideais da ECP, antes que as complicações da DP se tornem irreversíveis. O objetivo desta primeira parte da revisão é examinar os conceitos fundamentais da ECP na prática clínica, discutindo os aspectos históricos, a seleção de pacientes, os potenciais efeitos da ECP nos sintomas motores e não motores da doença e o manejo prático dos pacientes após a cirurgia.

Processamento auditivo central e questionário de autopercepção pós-treinamento auditivo acusticamente controlado em indivíduos com traumatismo cranioencefálico leve / Central auditory processing and self-perception questionnaire after acoustically controlled auditory training in individuals with mild traumatic brain injury

RESUMO Objetivo Correlacionar os resultados da avaliação comportamental do processamento auditivo central e do questionário de autopercepção após o treinamento auditivo acusticamente controlado. Método Foram avaliados dez indivíduos com média de idade de 44,5 anos, que sofreram traumatismo cranioencefálico de grau leve. Os indivíduos foram submetidos a avaliação comportamental do processamento auditivo central e também responderam ao questionário de autopercepção "Treinamento Auditivo Formal" após a intervenção terapêutica. O questionário foi composto por questões referentes a percepção auditiva, compreensão de ordens, solicitação de repetição de enunciados, ocorrência mal-entendidos, tempo de atenção, desempenho auditivo em ambiente ruidoso, comunicação ao telefone e autoestima e os pacientes foram solicitados a assinalar a frequência de ocorrência dos comportamentos listados. Resultados As habilidades auditivas de figura-fundo e memória para sons em sequência e processamento temporal correlacionaram-se com melhora para seguir instruções, diminuição das solicitações de repetições e aumento do tempo de atenção e melhora da comunicação e da compreensão ao telefone e para assistir TV. Conclusão Observou-se adequação das habilidades auditivas de fechamento auditivo, figura fundo, e processamento temporal na avaliação pós-treinamento auditivo acusticamente controlado, além de redução das queixas quanto ao comportamento auditivo.

ABSTRACT Purpose To correlate behavioral assessment results of central auditory processing and the self-perception questionnaire after acoustically controlled auditory training. Methods The study assessed 10 individuals with a mean age of 44.5 years who had suffered mild traumatic brain injury. They underwent behavioral assessment of central auditory processing and answered the Formal Auditory Training self-perception questionnaire after the therapeutic intervention - whose questions address auditory perception, understanding orders, request to repeat statements, occurrence of misunderstandings, attention span, auditory performance in noisy environments, telephone communication, and self-esteem. Patients were asked to indicate the frequency with which the listed behaviors occurred. Results Figure-ground, sequential memory for sounds, and temporal processing correlated with improvement in following instructions, fewer requests to repeat statements, increased attention span, improved communication, and understanding on the phone and when watching TV. Conclusion Auditory closure, figure-ground, and temporal processing had improved in the assessment after the acoustically controlled auditory training, and there were fewer auditory behavior complaints.

The uniqueness of the human brain: a review / A singularidade do cérebro humano: uma revisão

ABSTRACT The purpose of this review is to highlight the most important aspects of the anatomical and functional uniqueness of the human brain. For this, a comparison is made between our brains and those of our closest ancestors (chimpanzees and bonobos) and human ancestors. During human evolution, several changes occurred in the brain, such as an absolute increase in brain size and number of cortical neurons, in addition to a greater degree of functional lateralization and anatomical asymmetry. Also, the cortical cytoarchitecture became more diversified and there was an increase in the number of intracortical networks and networks extending from the cerebral cortex to subcortical structures, with more neural networks being invested in multisensory and sensory-motor-affective-cognitive integration. These changes permitted more complex, flexible and versatile cognitive abilities and social behavior, such as shared intentionality and symbolic articulated language, which, in turn, made possible the formation of larger social groups and cumulative cultural evolution that are characteristic of our species.

RESUMO Esta revisão se propõe a relatar os aspectos mais importantes da singularidade anatômica e funcional do cérebro humano. Para isso, faz-se uma comparação entre o nosso cérebro e os de nossos parentes evolutivos mais próximos (chimpanzés e bonobos) e os ancestrais humanos. Durante a evolução humana ocorreu aumento absoluto do tamanho do cérebro e do número de neurônios corticais cerebrais, maior grau de lateralização funcional e assimetria anatômica cerebral, citoarquitetura cortical mais diversificada e aumento das redes neurais intracorticais e do córtex cerebral para as estruturas subcorticais acompanhada de mudança em direção ao investimento de redes neurais na integração multissensorial e sensório-motora-afetiva-cognitiva. Essas mudanças possibilitaram capacidades cognitivas e comportamentos sociais complexos, flexíveis e versáteis, destacando-se a intencionalidade compartilhada e a linguagem articulada simbólica, que permitiram a formação de grupos sociais maiores e a evolução cultural cumulativa característica de nossa espécie.

Why did humans surpass all other primates? Are our brains so different? Part 1 / Por que os seres humanos superaram todos os outros primatas? Nossos cérebros são tão diferentes? Parte 1

ABSTRACT. This review is based on a conference presented in June 2023. Its main objective is to explain the cognitive differences between humans and non-human primates (NHPs) focusing on characteristics of their brains. It is based on the opinion of a clinical neurologist and does not intend to go beyond an overview of this complex topic. As language is the main characteristic differentiating humans from NHPs, this review is targeted at their brain networks related to language. NHPs have rudimentary forms of language, including primitive lexical/semantic signs. Humans have a much broader lexical/semantic repertory, but syntax is the most important characteristic, which is probably unique to Homo sapiens. Angular gyrus, Broca's area, temporopolar areas, and arcuate fascicle, are much more developed in humans. These differences may explain why NHPs did not develop a similar language to ours. Language had a profound influence on all other higher nervous activities.

RESUMO Esta revisão baseia-se numa conferência apresentada em junho de 2023. O seu principal objetivo é explicar as diferenças cognitivas entre humanos e primatas não humanos (PNH) com base nas características dos seus cérebros. Baseia se na opinião de um neurologista clínico e não pretende ir além de uma visão geral deste tema complexo. Como a linguagem é a principal característica que diferencia os humanos dos PNH, esta revisão concentra-se nas redes cerebrais relacionadas à linguagem. Os PNH têm formas rudimentares de linguagem, incluindo sinais lexicais/semânticos primitivos. Os humanos têm um repertório léxico/semântico muito mais amplo, mas a sintaxe é a característica mais importante e única do Homo sapiens. O giro angular, a área de Broca, as áreas temporopolares e o fascículo arqueado são muito mais desenvolvidos em humanos. Essas diferenças podem explicar por que os PNH não desenvolveram uma linguagem semelhante à nossa. A linguagem teve influência profunda em todas as outras atividades nervosas superiores.

Expression of brain-derived neurotrophic factor and formation of migrasome increases in the glioma cells induced by the adipokinetic hormone

SUMMARY OBJECTIVE: It has been previously shown that brain-derived neurotrophic factor is linked with various types of cancer. Brain-derived neurotrophic factor is found to be highly expressed in multiple human cancers and associated with tumor growth, invasion, and metastasis. Adipokinetic hormones are functionally related to the vertebrate glucagon, as they have similar functionalities that manage the nutrient-dependent secretion of these two hormones. Migrasomes are new organelles that contain numerous small vesicles, which aid in transmitting signals between the migrating cells. Therefore, the aim of this study was to investigate the effects of Anax imperator adipokinetic hormone on brain-derived neurotrophic factor expression and ultrastructure of cells in the C6 glioma cell line. METHODS: The rat C6 glioma cells were treated with concentrations of 5 and 10 Anax imperator adipokinetic hormone for 24 h. The effects of the Anax imperator adipokinetic hormone on the migrasome formation and brain-derived neurotrophic factor expression were analyzed using immunocytochemistry and transmission electron microscope. RESULTS: The rat C6 glioma cells of the 5 and 10 μM Anax imperator adipokinetic hormone groups showed significantly high expressions of brain-derived neurotrophic factor and migrasomes numbers, compared with the control group. CONCLUSION: A positive correlation was found between the brain-derived neurotrophic factor expression level and the formation of migrasome, which indicates that the increased expression of brain-derived neurotrophic factor and the number of migrasomes may be involved to metastasis of the rat C6 glioma cell line induced by the Anax imperator adipokinetic hormone. Therefore, the expression of brain-derived neurotrophic factor and migrasome formation may be promising targets for preventing tumor proliferation, invasion, and metastasis in glioma.

Evaluation of the maturational auditory process in children with the infection by Zika congenital syndrome / Avaliação do processo maturacional auditivo em crianças portadoras da síndrome da infecção congênita pelo Zika vírus

ABSTRACT Purpose: to analyze the absolute latencies of waves I. III and V and the interpeak intervals I-III. III-V and I-V of the ABR recorded from different age groups of children with congenital zika virus infection and their peers without risk indicators for hearing impairment. Methods: 84 newborns and infants (N=51 study group and N=33 control group) divided into groups with different post-conceptual ages. with the results of their hearing exams analyzed by age group and compared with their peers without other risk indicators for hearing impairment. The assessment of the auditory pathway was conducted through tympanometry. otoacoustic emissions and auditory brain stem responses. Results: only the latency of wave I and the interpeak III-V showed no significant difference between the study and control groups. The absolute latency and interpeak values found in the study group were significantly lower than those found in the control group. Conclusion: the maturation of the brain stem in children with ZIKV infection occurred within normal limits. with no retrocochlear disorders until the age of 5 years.

RESUMO Objetivo: analisar as latências absolutas das ondas I. III e V e os intervalos interpicos I-III. III-V e I-V do Potencial Evocado Auditivo de Tronco Encefálico obtidos em diversos grupos etários de crianças portadoras de infecção congênita por zika vírus e nos seus pares sem indicadores de risco para deficiência auditiva. Métodos: foram recrutados 84 recém-nascidos e lactentes (N=51 grupo de estudo e N=33 grupo controle) separados por grupos com diferentes idades pós-conceptuais. sendo os resultados dos seus exames auditivos analisados por faixa etária e comparados com seus pares sem outros indicadores de risco para deficiência auditiva. A avaliação da via auditiva foi realizada por meio da timpanometria. emissões otoacústicas transientes e potencial evocado de tronco encefálico. Resultados: somente a latência da onda I e o intervalo interpico III-V não apresentaram diferença significante entre grupo de estudo e controle. Os valores de latências absolutas e interpicos encontrados no grupo de estudo foram menores do que os obtidos no grupo controle de forma significativa. Conclusão: a maturação do tronco encefálico nas crianças portadoras de infecção por Zika Vírus ocorreu dentro da normalidade. não apresentando alterações retrococleares até a idade de 5 anos.

The importance of basic and translational research in caring for children with malignant solid tumors in Latin America / La importancia de la investigación básica y aplicada para la atención de pacientes pediátricos con tumores sólidos malignos en América Latina / A importância da pesquisa básica e translacional no tratamento de crianças com tumores sólidos malignos na América Latina

ABSTRACT Objective. Basic and translational research in pediatric cancer are essential to improve patient care. To critically assess the developments achieved in these areas in Latin America, we systematically reviewed information published between 2013 and 2023. Methods. Studies of basic and translational research performed by investigators in Latin America evaluating pediatric malignant solid and central nervous system tumors were retrieved from PubMed. Original articles published in English between 2013 and 2023 were included. Collaborations among Latin American authors or among Latin American authors working with researchers from other continents were also included. Studies were excluded if they focused only on adults or on basic research in tumor biology not specifically related to the tumor types analyzed in this review. Results. A total of 550 articles were retrieved, but after removal of duplicates, 514 articles were included in the analysis, the majority of which were authored by researchers affiliated with institutions in Argentina, Brazil and Mexico. These countries also had the highest number of collaborations on original articles published with authors from Europe and North America. Argentina had the highest number of collaborations on original publications, with coauthors from Brazil and Uruguay. The median impact factor of the 244 journals in which articles were published was 3.5. The most commonly studied tumors were osteosarcomas, neuroblastomas and medulloblastomas; the most commonly studied areas were molecular analysis, tumor cell biology and biomarkers. Conclusions. In Latin America, research in pediatric oncology is on the agenda, despite a notable disparity in publication rates and frequency of collaboration between countries. There is a need to strengthen scientific collaboration within Latin America and with countries from other continents to promote research and to develop novel treatment strategies that reflect the local needs of children in Latin America who have solid tumors and brain cancer.

RESUMEN Objetivo. La investigación básica y aplicada en el campo de la oncología pediátrica es fundamental para mejorar la atención al paciente. Con el objetivo de realizar una evaluación crítica de los avances logrados en este campo en América Latina, hemos realizado una revisión sistemática de la información publicada entre el 2013 y el 2023. Metodología. Se recopilaron de PubMed los artículos de investigación básica y traslacional publicados por investigadores de América Latina en los que se evaluaron tumores malignos sólidos y del sistema nervioso central en la población infantil. Se incluyeron artículos originales publicados en inglés entre el 2013 y el 2023. También se incluyeron artículos fruto de la colaboración científica entre autores e investigadores de América Latina y otros continentes. Se excluyeron aquellos estudios que se centraron solo en personas adultas o en la investigación básica en biología tumoral no relacionada específicamente con los tipos de tumores analizados en esta revisión. Resultados. Se encontraron 550 artículos en total. Después de eliminar los artículos duplicados, se incluyeron 514 artículos en la revisión, la mayoría de los cuales fueron escritos por investigadores vinculados a centros de investigación de Argentina, Brasil y México. También procedieron de estos tres países la mayor parte de los artículos originales escritos en colaboración con autores de Europa y América del Norte. Argentina tuvo el mayor número de colaboraciones en publicaciones originales, con coautores de Brasil y Uruguay. La mediana del índice de impacto de las 244 revistas en las que se publicaron los artículos fue de 3,5. Los tumores más estudiados fueron osteosarcomas, neuroblastomas y meduloblastomas. Los temas más estudiados fueron el análisis molecular, la biología de las células tumorales y los biomarcadores. Conclusiones. La investigación en oncología pediátrica forma parte de la agenda de investigación de América Latina, si bien hay una disparidad notoria en las tasas de publicación y la frecuencia de la colaboración entre países. Es necesario fortalecer la colaboración científica dentro de América Latina y con los países de otros continentes para promover la investigación y desarrollar estrategias de tratamiento novedosas que respondan a las necesidades locales de los niños y niñas de América Latina que tienen tumores sólidos o cáncer del sistema nervioso central.

RESUMO Objetivo. A pesquisa básica e translacional em câncer pediátrico é essencial para melhorar o atendimento dos pacientes. No intuito de realizar uma avaliação crítica dos avanços alcançados nessa área na América Latina, fez-se uma revisão sistemática de informações publicadas entre 2013 e 2023. Métodos. Pesquisas básicas e translacionais realizadas por pesquisadores da América Latina que avaliaram tumores sólidos malignos e tumores do sistema nervoso central em crianças foram obtidas da base de dados PubMed. Foram incluídos artigos originais publicados em inglês entre 2013 e 2023. Também foram incluídas colaborações entre autores latino-americanos ou entre autores latino-americanos que trabalham com pesquisadores de outros continentes. Estudos que tratavam apenas de adultos ou pesquisas básicas sobre biologia tumoral não especificamente relacionadas aos tipos de tumor analisados nesta revisão foram excluídos. Resultados. No total, a busca recuperou 550 artigos da base de dados. Após a remoção dos artigos duplicados, foram incluídos 514 artigos na análise, a maioria de autoria de pesquisadores de instituições da Argentina, do Brasil e do México. Esses países também tiveram o maior número de colaborações em artigos originais publicados com autores da Europa e da América do Norte. A Argentina teve o maior número de colaborações em publicações originais, com coautores do Brasil e do Uruguai. O fator de impacto mediano dos 244 periódicos nos quais os artigos foram publicados era de 3,5. Os tumores mais estudados foram osteossarcomas, neuroblastomas e meduloblastomas; as áreas mais estudadas foram análise molecular, biologia de células tumorais e biomarcadores. Conclusões. Na América Latina, a pesquisa em oncologia pediátrica está na ordem do dia, apesar de uma evidente disparidade nos índices de publicação e na frequência de colaboração entre os países. É necessário fortalecer a colaboração científica dentro da América Latina e com países de outros continentes a fim de promover a pesquisa e desenvolver novas estratégias de tratamento que reflitam as necessidades locais das crianças latino-americanas com tumores sólidos e câncer cerebral.

Treatment of Parkinson's disease by deep brain stimulation: a bibliometric analysis

ABSTRACT BACKGROUND: For more than 30 years, deep brain stimulation (DBS) has been a therapeutic tool for Parkinson's disease (PD) treatment. DBS can ameliorate several motor and non-motor symptoms and improve the patients' quality of life. OBJECTIVES: To analyze the global scientific production of original and review articles on Parkinson's disease treatment using deep brain stimulation. DESIGN AND SETTING: Descriptive, bibliometric study with a quantitative approach. METHOD: The research protocol was conducted in March 2023 using the Web of Science database. Six hundred eighty-four articles were included in the analysis. Data were imported into RStudio Desktop Software, linked to R Software. The Bibliometrix R package, its Biblioshiny web interface, and VOSviewer software were used for the analysis. RESULTS: The international production began in 1998. Movement Disorders is the journal with the largest number of published articles and the most cited. Michael Okun and Andres Lozano are the authors who produced the most in this area. The University of Florida is the most active affiliated institution in Brazil. The United States has the largest number of collaborations and is mainly published by local researchers. In contrast, countries such as the United Kingdom and Canada have a high number of multi-country publications. The 15 most cited studies predominantly investigated subthalamic nucleus stimulation. CONCLUSION: DBS for Parkinson's disease is a relatively novel therapeutic approach, with studies that have expanded over the last twenty-five years. Most scientific production was quantitative and restricted to specialized journals. The United States, Europe, and China held the most articles.

Brain insulin resistance and Alzheimer's disease: a systematic review / Resistência insulínica cerebral e a doença de Alzheimer: uma revisão sistemática

ABSTRACT. The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been well-researched in organs such as adipose tissue, muscle, and liver, has been linked to neurodegenerative diseases like Alzheimer's disease (AD) when it occurs in the brain. Objective: The authors aimed to gather data from the current literature on brain insulin resistance (BIR) and its likely repercussions on neurodegenerative disorders, more specifically AD, through a systematic review. Methods: A comprehensive search was conducted in multiple medical databases, including the Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline), and PubMed®, employing the descriptors: "insulin resistance", "brain insulin resistance", "Alzheimer's disease", "neurodegeneration", and "cognition". The authors focused their search on English-language studies published between 2000 and 2023 that investigated the influence of BIR on neurodegenerative disorders or offered insights into BIR's underlying mechanisms. Seventeen studies that met the inclusion criteria were selected. Results: The results indicate that BIR is a phenomenon observed in a variety of neurodegenerative disorders, including AD. Studies suggest that impaired glucose utilization and uptake, reduced adenosine triphosphate (ATP) production, and synaptic plasticity changes caused by BIR are linked to cognitive problems. However, conflicting results were observed regarding the association between AD and BIR, with some studies suggesting no association. Conclusion: Based on the evaluated studies, it can be concluded that the association between AD and BIR remains inconclusive, and additional research is needed to elucidate this relationship.

RESUMO. A incapacidade das células de reagir à insulina, ocasionando intolerância à glicose e hiperglicemia, é chamada de resistência à insulina. Essa condição clínica, que tem sido bem pesquisada em órgãos como tecido adiposo, músculo e fígado, tem sido associada às doenças neurodegenerativas como a doença de Alzheimer (DA) quando ocorre no cérebro. Objetivo: O objetivo dos autores foi reunir os dados da literatura atual sobre a resistência insulínica cerebral (RIC) e sua provável repercussão em doenças neurodegenerativas, mais especificamente na DA, por meio de uma revisão sistemática da literatura. Métodos: Foi realizada uma pesquisa abrangente em vários bancos de dados médicos, incluindo o Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline) e PubMed, empregando os descritores: "resistência à insulina", "resistência insulínica cerebral", "doença de Alzheimer", "neurodegeneração" e "cognição". Os autores concentraram sua busca em estudos no idioma inglês publicados entre 2000 e 2023 que investigaram a influência da RIC em distúrbios neurodegenerativos ou ofereceram insights sobre os mecanismos subjacentes da RIC. Dezessete estudos que atenderam aos critérios de inclusão foram selecionados. Resultados: Os resultados demonstram que a RIC é um fenômeno observado em uma variedade de doenças neurodegenerativas, incluindo a DA. Estudos sugerem que a utilização e captação prejudicadas de glicose, a produção reduzida de trifosfato de adenosina (ATP) e as alterações na plasticidade sinápticas causadas pela RIC estão ligadas a problemas cognitivos. No entanto, foram observados resultados conflitantes com relação à associação entre DA e RIC, com alguns estudos sugerindo nenhuma associação. Conclusão: Com base nos estudos avaliados, pode-se concluir que a associação entre DA e RIC ainda é inconclusiva, e pesquisas adicionais são necessárias para elucidar essa relação.

Dor neuropática: sentimentos e vivências de pacientes após lesões traumáticas / Neuropathic pain: feelings and experiences of patients after traumatic injuries / Dolor neuropático: sentimientos y experiencias de pacientes después lesiones traumáticas

Objetivo: Compreender o cotidiano de portadores de dor neuropática decorrente de lesão traumática. Metodologia: Pesquisa exploratória, descritiva, de abordagem qualitativa, com participantes selecionados por meio de mídias sociais. A coleta de dados foi realizada entre o período de julho a setembro de 2022, com indivíduos adultos que possuem diagnóstico de dor neuropática após lesão traumática. A coleta ocorreu por meio de um formulário online, utilizando um questionário sociodemográfico e um questionário aberto, para a captura de informações pertinentes sobre seu caso clínico e vivência com a dor crônica. Os dados foram analisados por meio de Bardin. Todos os preceitos éticos foram respeitados e o projeto foi aprovado sob parecer n.º 5.529.581 da Universidade Cesumar. Resultados: Participaram 15 pessoas com dor neuropática, com prevalência do sexo feminino (93,3%), com idade entre 41 a 50 anos (66,7%). Observou-se que 53,3% relataram comorbidades crônicas, sendo as doenças psíquicas, ansiolíticas e cardíacas mais citadas. Ainda, 33,3% dos participantes relataram que foram internados por causas de dores ou por tentativa de suicídio, 93,3% usam opióides e analgésicos potentes e ainda foram citados antidepressivos e ansiolíticos em 62% das respostas. Dentre os temas em destaque nas respostas, sobressaíram-se "Contexto e diagnóstico da dor neuropática; Vivência e frequência da dor; Apoio profissional e familiar diante da doença". Considerações Finais: Nesse sentido, a percepção acerca dos profissionais de saúde e valorização do médico para o tratamento da dor neuropática está relacionada, muitas vezes, à necessidade de aumentar o conhecimento referente ao manejo da dor e à utilização de opióides.

Objective: To understand the daily life of patients with neuropathic pain resulting from traumatic injury. Methodology: Exploratory, descriptive research, with a qualitative approach, with participants selected through social media. Data collection was carried out between July and September 2022, with adult individuals diagnosed with neuropathic pain after traumatic injury. The collection took place through an online form, using a sociodemographic questionnaire and an open questionnaire, to capture relevant information about their clinical case and experience with chronic pain. Data were analyzed using Bardin. All ethical precepts were respected and the project was approved by report n.º 5,529,581 of Cesumar University. Results: 15 people with neuropathic pain participated, with a prevalence of females (93.3%), aged between 41 and 50 years (66.7%). It was observed that 53.3% reported chronic comorbidities, with psychic, anxiolytic and cardiac diseases being the most cited. Also, 33.3% of the participants reported that they were hospitalized due to pain or a suicide attempt, 93.3% used opioids and potent analgesics, and antidepressants and anxiolytics were mentioned in 62% of the answers. Among the topics highlighted in the responses, the most important were "Context and diagnosis of neuropathic pain; Experience and frequency of pain; Professional and family support in the face of the disease". Final Considerations: In this sense, the perception of health professionals and the appreciation of physicians for the treatment of neuropathic pain is often related to the need to increase knowledge regarding pain management and the use of opioids.

Objetivo: Comprender el cotidiano de los pacientes con dolor neuropático resultante de lesiones traumáticas. Metodología: Investigación exploratoria, descriptiva, con enfoque cualitativo, con participantes seleccionados a través de las redes sociales. La recolección de datos se llevó a cabo entre julio y septiembre de 2022, con individuos adultos diagnosticados con dolor neuropático posterior a una lesión traumática. La recogida se realizó a través de un formulario online, utilizando un cuestionario sociodemográfico y un cuestionario abierto, para captar información relevante sobre su caso clínico y experiencia con el dolor crónico. Los datos se analizaron utilizando Bardin. Se respetaron todos los preceptos éticos y el proyecto fue aprobado bajo el dictamen número 5.529.581 de la Universidad Cesumar. Resultados: Participaron 15 personas con dolor neuropático, con predominio del sexo femenino (93,3%), con edades entre 41 y 50 años (66,7%). Se observó que 53,3% relataron comorbilidades crónicas, siendo las enfermedades psíquicas, ansiolíticas y cardíacas las más citadas. Aún así, el 33,3% de los participantes informaron que fueron hospitalizados por dolor o intento de suicidio, el 93,3% usaba opioides y analgésicos potentes, y los antidepresivos y ansiolíticos se mencionaron en el 62% de las respuestas. Entre los temas destacados en las respuestas, los más importantes fueron "Contexto y diagnóstico del dolor neuropático; Experiencia y frecuencia del dolor; Apoyo profesional y familiar ante la enfermedad". Consideraciones Finales: En este sentido, la percepción de los profesionales de la salud y la apreciación de los médicos por el tratamiento del dolor neuropático muchas veces se relaciona con la necesidad de aumentar el conocimiento sobre el manejo del dolor y el uso de opioides.

Primary somesthetic cortex involvement in fibromyalgia: review of neuroimage studies / Envolvimento do córtex somestésico primário na fibromialgia: revisão de estudos de neuroimagem

ABSTRACT BACKGROUND AND OBJECTIVES: The mechanisms underlying nociplastic pain, such as fibromyalgia (FM), are not fully understood, however, it is believed that altered sensory processing and pain modulation play prominent roles in the maintenance of nociplastic pain. The hypothesis is that changes in the primary somesthetic cortex (S1) contribute to the generalized pain character of FM. The objective of this study was to evaluate the involvement of the primary somesthetic cortex in humans with fibromyalgia, as well as to investigate possible associations between S1 changes and clinical signs and symptoms of FM. CONTENTS: For this integrative review, the following databases were used: Pubmed and Web of Science, including observational studies carried out in humans with FM. In total, 541 studies were identified and four were included. The majority of studies are case-control studies, published between 2016 and 2022. In total, data from 161 individuals were included in this review. It was identified that there are morphological changes, hyperactivation and increased functional connectivity between S1 and periaqueductal gray matter and between S1 and anterior cingulate cortex. CONCLUSION: Patients with FM present morphological changes and hyperactivation in S1, as well as increased functional connectivity between S1 and periaqueductal gray matter and S1 and limbic system. Furthermore, different bilateral somatotropic subregions (legs, chest, fingers, hands, face and back) showed reduced functional connectivity in patients with FM. These regions are often presented as "tender points" in FM.

RESUMO JUSTIFICATIVA E OBJETIVOS: Os mecanismos subjacentes à dor nociplástica, como a fibromialgia (FM), não são totalmente compreendidos, contudo acredita-se que o processamento sensorial e a modulação da dor alterados desempenham papéis proeminentes para a manutenção da dor nociplástica. Com a hipótese de que alterações no córtex somestésico primário (S1) contribuam para o caráter de dor generalizada da FM, o objetivo deste estudo foi avaliar o envolvimento do córtex somestésico primário em humanos com FM, bem como investigar possíveis associações entre alterações de S1 com sinais e sintomas clínicos da FM. CONTEÚDO: Para esta revisão integrativa, foram utilizadas as seguintes bases de dados: Pubmed e Web of Science, incluindo estudos observacionais realizados em humanos com FM. No total, 541 estudos foram identificados e quatro foram incluídos. A maioria dos estudos são do tipo caso-controle, publicados entre 2016 e 2022. Ao todo, dados de 161 indivíduos foram incluídos. Foi identificado que há alterações morfológicas, hiperativação e aumento da conectividade funcional entre S1 e substância cinzenta periaquedutal e entre S1 e córtex cingulado anterior. CONCLUSÃO: Pacientes com FM apresentam alterações morfológicas e hiperativação em S1, bem como aumento da conectividade funcional entre S1 e substância cinzenta periaquedutal e S1 e sistema límbico. Ademais, diferentes sub-regiões somatotrópicas bilaterais (pernas, tórax, dedos, mãos, face e costas) apresentaram redução da conectividade funcional em pacientes com FM. Essas regiões são frequentemente apresentadas como "tender points" na FM.

Prevalence of brain fag syndrome and its correlation with stimulant use and socioeconomic/demographic characteristics among university undergraduate students in Nigeria

Background: Brain Fag Syndrome (BFS) is a culture-bound syndrome characterized by cognitive and somatic symptoms, commonly reported among African students. This study aimed to determine the prevalence of BFS among Nigerian university students and examine its associated factors. Methods: A cross-sectional survey was conducted among undergraduate students from a university in the northwest region of Nigeria. The study utilized a self-administered questionnaire to collect data on socio-demographic characteristics, stimulant use, course of study, and academic performance. The presence of BFS was assessed using standardized diagnostic criteria. Results:The study included a total of 625 participants, in their young adulthood. The prevalence of BFS among Nigerian university students was found to be 62.7%. The majority of affected students were aged 20-30, male, and from the Hausa ethnic group. No significant association was found between stimulant use and BFS. However, there was a significant relationship between the course of study and the occurrence of BFS. Academic performance (CGPA) showed a weak negative association with BFS. Other socio-demographic factors such as age, gender, ethnicity, relationship status, birth position, type of home, and family income did not predict the occurrence of BFS. Conclusion: The high prevalence highlights the need for attention to mental health issues among this population. The results emphasize the importance of considering the course of study and academic performance when studying BFS. Further research is warranted to explore the underlying mechanisms and develop effective interventions for students affected by BFS.

Apport de l'IRM multimodale dans la prise en charge des tumeurs encéphaliques chez l'adulte à Abidjan / Contribution of multimodal MRI in the management of brain tumors in adults in Abidjan

Dans le monde, le nombre de nouveaux cas de tumeurs encéphaliques était de 14 millions en 2014 avec environ 8 millions de personnes décédées. Objectif: déterminer l'efficacité diagnostique de l'IRM multimodale dans la prise en charge des tumeurs encéphaliques dans notre contexte. Matériels et Méthodes: Etude rétrospective à visée descriptive, multicentrique sur une période de 2 ans allant de février 2017 à mars 2019, dans 2 services de radiologie et 2 services de Neurochirurgie, à Abidjan. Nous nous sommes intéressés àtous les patients ayant réalisé une IRM multimodale pour suspicion d'un processus tumoral encéphalique, et qui ont eu une exérèse chirurgicale suivie d'un examen anatomopathologique de la pièce opératoire. Les examens d'IRM multimodale encéphaliques ont été réalisés selon un protocole standard sur des appareils de 1,5 Tesla, et lus par des radiologues séniors. Nous avons confronté les résultats anatomopathologiques aux diagnostics posés à l'imagerie IRM multimodale.Résultats: Ont été retenu 18 dossiers. On notait une prédominance masculine avec un sex-ratio de 1,57. L'âge moyen était de 42,8 ans avec des extrêmes de 20ans et 61ans et un écart type de 10,75.La corrélation diagnostique entre l'examen anatomopathologique et l'IRM a été de6 sur 7 cas, 4 sur 5 cas, 2 sur 2 cas, 2 sur 2 cas et 1 sur 1 cas respectivement pour le méningiome, le gliome, les métastases, l'adénome hypophysaire, le lymphome cérébral primitif.Conclusion:Les tumeurs encéphaliques dans notre étude, étaient variéeset concernaient la population jeune. Les motifs d'erreur diagnostique étaient essentiellement en rapport avec la variété de présentations des tumeurs à l'IRM et l'expérience récente de nos radiologues sur l'utilisation efficace des séquences avancées.

Worldwide, the number of new cases of brain tumors was 14 million in 2014 with approximately 8 million people dying.Objective: determine the diagnostic effectiveness of multimodal MRI in the management of brain tumors in our context.Methods: Retrospective study with a descriptive aim, multicenter over a period of 2 years from February 2017 to March 2019, in 2 radiology departments and 2 neurosurgery departments, in Abidjan. We were interested in all patients who had a multimodal MRI for suspicion of a brain tumor process, and who had a surgical excision followed by an pathological examination of the surgical specimen. The multimodal brain MRI examinations were carried out according to a standard protocol on 1.5 Tesla devices, and read by seniorradiologists. We compared the pathological results with the diagnoses made on multimodal MRI imaging.Results:18 files were retained. There was a male predominance with a sex ratio of 1.57. The average age was 42.8 years with extremes of 20 and 61 years and a standard deviation of 10.75. The diagnostic correlation between the pathological examination and MRI was 6 out of 7 cases, 4 out of 5 cases, 2 out of 2 cases, 2 out of 2 cases and 1 out of 1 case respectively for meningioma, glioma, metastases, pituitary adenoma, primary cerebral lymphoma.Conclusion: The brain tumors in our study were varied and concerned the young population. The reasons for diagnostic error were mainly related to the variety of tumor presentations on MRI and the recent experience of our radiologists on the effective use of advanced sequences.

Mechanisms of brain damage caused by inorganic fluoride using proteomics-based techniques / 环境与职业医学

Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L−1), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L−1), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg−1). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

Mechanism of Yiqi Jiedu Formula Against Ischemic Stroke Based on Microbial-gut-brain Axis / 中国实验方剂学杂志

ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.