From Parametric Representation to Dynamical System: Shifting Views of the Motor Cortex in Motor Control / 神经科学通报·英文版

In contrast to traditional representational perspectives in which the motor cortex is involved in motor control via neuronal preference for kinetics and kinematics, a dynamical system perspective emerging in the last decade views the motor cortex as a dynamical machine that generates motor commands by autonomous temporal evolution. In this review, we first look back at the history of the representational and dynamical perspectives and discuss their explanatory power and controversy from both empirical and computational points of view. Here, we aim to reconcile the above perspectives, and evaluate their theoretical impact, future direction, and potential applications in brain-machine interfaces.

Formation of the Looming-evoked Innate Defensive Response during Postnatal Development in Mice / 神经科学通报·英文版

Environmental threats often trigger innate defensive responses in mammals. However, the gradual development of functional properties of these responses during the postnatal development stage remains unclear. Here, we report that looming stimulation in mice evoked flight behavior commencing at P14-16 and had fully developed by P20-24. The visual-evoked innate defensive response was not significantly altered by sensory deprivation at an early postnatal stage. Furthermore, the percentages of wide-field and horizontal cells in the superior colliculus were notably elevated at P20-24. Our findings define a developmental time window for the formation of the visual innate defense response during the early postnatal period and provide important insight into the underlying mechanism.

Ventromedial Thalamus-Projecting DCN Neurons Modulate Associative Sensorimotor Responses in Mice / 神经科学通报·英文版

The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCNVm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCNVm neurons' function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.

Modulation of Spike Count Correlations Between Macaque Primary Visual Cortex Neurons by Difficulty of Attentional Task / 神经科学通报·英文版

Studies have shown that spatial attention remarkably affects the trial-to-trial response variability shared between neurons. Difficulty in the attentional task adjusts how much concentration we maintain on what is currently important and what is filtered as irrelevant sensory information. However, how task difficulty mediates the interactions between neurons with separated receptive fields (RFs) that are attended to or attended away is still not clear. We examined spike count correlations between single-unit activities recorded simultaneously in the primary visual cortex (V1) while monkeys performed a spatial attention task with two levels of difficulty. Moreover, the RFs of the two neurons recorded were non-overlapping to allow us to study fluctuations in the correlated responses between competing visual inputs when the focus of attention was allocated to the RF of one neuron. While increasing difficulty in the spatial attention task, spike count correlations were either decreased to become negative between neuronal pairs, implying competition among them, with one neuron (or none) exhibiting attentional enhancement of firing rate, or increased to become positive, suggesting inter-neuronal cooperation, with one of the pair showing attentional suppression of spiking responses. Besides, the modulation of spike count correlations by task difficulty was independent of the attended locations. These findings provide evidence that task difficulty affects the functional interactions between different neuronal pools in V1 when selective attention resolves the spatial competition.

Entrainment of Astrocytic and Neuronal Ca2+ Population Dynamics During Information Processing of Working Memory in Mice / 神经科学通报·英文版

Astrocytes are increasingly recognized to play an active role in learning and memory, but whether neural inputs can trigger event-specific astrocytic Ca2+ dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca2+ dynamics in animals performing tasks. Here, using fiber photometry, we showed that population astrocytic Ca2+ dynamics in the hippocampus were gated by sensory inputs (centered at the turning point of the T-maze) and modified by the reward delivery during the encoding and retrieval phases. Notably, there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca2+ dynamics with a 3-s phase difference. Furthermore, there was a robust synchronization of astrocytic Ca2+ at the population level among the hippocampus, medial prefrontal cortex, and striatum. The inter-locked, bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.

Changes in sensitivity of bilateral medial vestibular nuclear neurons responding to input stimuli during vestibular compensation and the underlying ionic mechanism / 生理学报

Vestibular compensation is an important model for developing the prevention and intervention strategies of vestibular disorders, and investigating the plasticity of the adult central nervous system induced by peripheral injury. Medial vestibular nucleus (MVN) in brainstem is critical center for vestibular compensation. Its neuronal excitability and sensitivity have been implicated in normal function of vestibular system. Previous studies mainly focused on the changes in neuronal excitability of the MVN in lesional side of the rat model of vestibular compensation following the unilateral labyrinthectomy (UL). However, the plasticity of sensitivity of bilateral MVN neurons dynamically responding to input stimuli is still largely unknown. In the present study, by using qPCR, whole-cell patch clamp recording in acute brain slices and behavioral techniques, we observed that 6 h after UL, rats showed a significant deficit in spontaneous locomotion, and a decrease in excitability of type B neurons in the ipsilesional rather than contralesional MVN. By contrast, type B neurons in the contralesional rather than ipsilesional MVN exhibited an increase in response sensitivity to the ramp and step input current stimuli. One week after UL, both the neuronal excitability of the ipsilesional MVN and the neuronal sensitivity of the contralesional MVN recovered to the baseline, accompanied by a compensation of spontaneous locomotion. In addition, the data showed that the small conductance Ca2+-activated K+ (SK) channel involved in the regulation of type B MVN neuronal sensitivity, showed a selective decrease in expression in the contralesional MVN 6 h after UL, and returned to normal level 1 week later. Pharmacological blockage of SK channel in contralateral MVN to inhibit the UL-induced functional plasticity of SK channel significantly delayed the compensation of vestibular motor dysfunction. These results suggest that the changes in plasticity of the ipsilesional MVN neuronal excitability, together with changes in the contralesional MVN neuronal sensitivity, may both contribute to the development of vestibular symptoms as well as vestibular compensation, and SK channel may be an essential ionic mechanism responsible for the dynamic changes of MVN neuronal sensitivity during vestibular compensation.

Rabbit vomeronasal organ-derivered cells have mesenchymal profile and neuronal commitment / Las células derivadas del órgano vomeronasal del conejo tienen perfil mesenquimatoso y compromiso neuronal

SUMMARY: The vomeronasal organ (VNO) is an accessory organ involved on the olfactory pathway, that detects pheromones and emits signals in order to modulate social and reproductive behavior. The VNO stem cells replace neurons throughout life. The aim of this study was to isolate and characterize cells derived from the vomeronasal organ from New Zealand rabbits. Five male rabbits with 120 days were used for cell isolation and culture. Results: VNO-derived cells presented labelling for proliferation (PCNA), undifferentiated profile (Nanog), neuronal (GFAP), mesenchymal stem cells (CD73, CD90 and CD105 and Stro-1). Also, presence of cytoskeletal (Vimentin, b-tubulin and CK-18) and absence of hematopoietic markers (CD34, CD117 and CD45) both by immunofluorescence and flow cytometry. By PCR it was possible to verify the expression of some undifferentiated profile (Oct-4), neuronal (Nestin) and mesenchymal (CD73, CD105 and Vimentin) genes. Functionally, VNO-derived cells differentiate in vitro into adipocytes, osteocytes and chondrocytes, and presented no tumorigenic potential when injected to Balb/c nu/nu mice. In conclusion, the rabbit VNO-derived cells have a profile that could be supportive to VNO olfactory/neuroreceptor epithelium by delivering factors to epithelial turnover or even by differentiation into epithelial cells to replacement of commissural epithelium.

RESUMEN: El órgano vomeronasal (OVN) es un órgano accesorio de la vía olfatoria, que detecta feromonas y emite señales que afectan la modulación del comportamiento social y reproductivo. Las células madre OVN reemplazan las neuronas durante toda la vida. El objetivo de este estudio fue aislar y caracterizar células derivadas del órgano vomeronasal de conejos raza Nueva Zelanda. Para el aislamiento y el cultivo celular se utilizaron cinco conejos machos con una edad de 120 días. Las células del OVN presentaron etiquetado para la proliferación (PCNA), un perfil indiferenciado (Nanog), neuronal (GFAP), células madre mesenquimales (CD73, CD90 y CD105 y Stro-1). Además, se ob- servó presencia de citoesqueleto (Vimentina, β-tubulina y CK-18) y ausencia de marcadores hematopoyéticos (CD34, CD117 y CD45) tanto por inmunofluorescencia como por citometría de flujo. Me- diante PCR fue posible verificar la expresión de algunos genes de perfil indiferenciado (Oct-4), neuronal (Nestin) y mesenquimatoso (CD73, CD105 y Vimentin). Las células derivadas del OVN se diferencian in vitro en adipocitos, osteocitos y condrocitos, y no presentan un potencial tumorigénico al ser infiltrados en ratones Balb / c nu / nu. En conclusión, las células derivadas de OVN de conejo tienen un perfil que podría ser compatible con el epitelio olfatorio / neurorreceptor de OVN transmitiendo factores al recambio epitelial o incluso mediante la diferenciación en células epiteliales para reemplazar el epitelio comisural.

Effect of periapical inflammation on calcium binding proteins and ERK in the trigeminal nucleus / Efecto de la inflamación periapical sobre las proteínas fijadoras de calcio y ERK en el núcleo trigeminal

Peripheral inflammation induces plastic changes in neurons and glia which are regulated by free calcium and calcium binding proteins (CaBP). One of the mechanisms associated with the regulation of intracellular calcium is linked to ERK (Extracellular Signal-Regulated Kinase) and its phosphorylated condition (pERK). ERK phosphorylation is important for intracellular signal transduction and participates in regulating neuroplasticity and inflammatory responses. The aim of this study is to analyse the expression of two CaBPs and pERK in astrocytes and neurons in rat trigeminal subnucleus caudalis (Vc) after experimental periapical inflammation on the left mandibular first molar. At seven days post-treatment, the periapical inflammatory stimulus induces an increase in pERK expression both in S100b positive astrocytes and Calbindin D28k positive neurons, in the ipsilateral Vc with respect to the contralateral side and control group. pERK was observed coexpressing with S100b in astrocytes and in fusiform Calbindin D28k neurons in lamina I. These results could indicate that neural plasticity and pain sensitization could be maintained by ERK activation in projection neurons at 7 days after the periapical inflammation.

La inflamación periférica induce cambios plásticos en las neuronas y en la glía, los cuales están regulados por el calcio libre y las proteínas fijadoras calcio (CaBP). Uno de los mecanismos asociados con la regulación del calcio intrace-lular está vinculado con la fosforilación de la pro teína quinasa ERK. Asimismo, ERK fosforilado es importante para la trans-ducción de señales intracelulares y participa en la regulación de la neuroplasticidad y las respuestas inflamatorias. El objetivo de este estudio es analizar la expresión de dos CaBPs y pERK en astrocitos y neuronas del subnúcleo caudal del trigémino (Vc) después de una inflamación periapical experimental en el primer molar inferior izquierdo en ratas. A los siete días posteriores al tratamiento, el estímulo inflamatorio periapical induce un aumento en la expresión de pERK, en el número de astrocitos positivos para la proteína marcadora astroglial S100b y en neuronas positivas para Calbindina D28k, en el Vc ipsilateral respecto del lado contralateral y el grupo de control. Además, se observó coexpresión de pERK tanto en astrocitos S100b positivos, como en neuronas fusiformes Calbindin D28k positivas, de la lámina I. Estas observaciones podrían indicar que la neuroplasticidad y la sensibilización al dolor podrían mantenerse mediante la activación de ERK en las neuronas de proyección a los 7 días de la inflamación periapical.

Comprendiendo el código neuronal: un análisis de cuatro perspectivas / Understanding the neural code: a four-perspective analysis

El objetivo de este artículo de revisión es dar a conocer diferentes perspectivas que han contribuido al estudio del Código Neuronal, un concepto que proviene de la Neurociencia y que explica el funcionamiento del cerebro a través de conexiones de neuronas. Se entregan cuatro ideas relacionadas con el análisis de este funcionamiento. En primer lugar, la propuesta de Convergencia Jerárquica, que ofrece una explicación asociada a un correlato neuronal específico para una conducta determinada. En segundo lugar, se aborda la idea del Código de Poblaciones, que explica el trabajo de un grupo de neuronas que representan un determinado estado. Posteriormente se expone la propuesta de Correlación Temporal, que plantea la presencia de poblaciones neuronales activas que se diferencian entre sí en base a patrones temporales de descarga para, finalmente, llegar al concepto de redes neuronales y sus diferentes modelos explicativos que han actuado como cimientos para el desarrollo de la Neurociencia moderna y que han sido desarrollados gracias a los aportes de la Biología, la Física, las Matemáticas, entre otras disciplinas, y que han generado las bases para la comprensión del funcionamiento del cerebro a través de neuronas interconectadas para lograr la expresión de los diferentes procesos cognitivos. El presente artículo pretende que el lector desarrolle una visión panorámica y general de cómo opera el flujo de la información que procesa el sistema nervioso central y el impacto que este fenómeno genera en el proceso de integración sensorial como parte de la emoción y la cognición en el cerebro humano.

The objective of this review article is to present different perspectives that have contributed to the study of the Neural Code, a concept that comes from Neuroscience and that explains the functioning of the brain through neuron connections. Four ideas related to the analysis of this functioning are presented. Firstly, the proposal of Hierarchical Convergence, which offers an explanation associated with a specific neuronal correlate for a specific behavior. Secondly, the idea of the Population Code is discussed, which explains the work of a group of neurons that represent a certain state. Subsequently, the proposal of Temporal Correlation is addressed, which proposes the presence of active neuronal populations that differentiate each other based on temporal discharge patterns, finally arriving at the concept of neural networks and their different explanatory models. The latter have acted as foundations for the development of modern Neuroscience and have been developed thanks to the contributions of Biology, Physics, Mathematics, among other disciplines, and have generated the basis for understanding the functioning of the brain through interconnected neurons to achieve the expression of the different cognitive processes. The paper aims to develop a panoramic and general view of how the flow of information processed by the central nervous system operates and the impact that this phenomenon generates in the process of sensory integration as part of emotion and cognition in the human brain.

Thiamine deficiency contributes to synapse and neural circuit defects

BACKGROUND: The previous studies have demonstrated the reduction of thiamine diphosphate is specific to Alzheimer's disease (AD) and causal factor of brain glucose hypometabolism, which is considered as a neurodegenerative index of AD and closely correlates with the degree of cognitive impairment. The reduction of thiamine diphosphate may contribute to the dysfunction of synapses and neural circuits, finally leading to cognitive decline. RESULTS: To demonstrate this hypothesis, we established abnormalities in the glucose metabolism utilizing thiamine deficiency in vitro and in vivo, and we found dramatically reduced dendrite spine density. We further detected lowered excitatory neurotransmission and impaired hippocampal long-term potentiation, which are induced by TPK RNAi in vitro. Importantly, via treatment with benfotiamine, Aß induced spines density decrease was considerably ameliorated. CONCLUSIONS: These results revealed that thiamine deficiency contributed to synaptic dysfunction which strongly related to AD pathogenesis. Our results provide new insights into pathogenesis of synaptic and neuronal dysfunction in AD.

Modelo in vitro para el estudio del papel de la unión mesopontina en la generación del sueño de movimientos oculares rápidos y la vigilia / In vitro model for the study of the role of the mesopontine region in rapid eye movement (REM) sleep and wakefulness / Modelo in vitro para o estudo do papel da união mesopontina na geração de sono de movimentos oculares rápidos e da vigília

El estudio de las estrategias neurales para la organización del comportamiento en vertebrados constituye un desafío mayor para la Neurociencia. El avance del conocimiento en este campo depende de manera crítica de la utilización de modelos experimentales adecuados que admitan múltiples niveles de análisis (p.ej: comportamental, circuital, celular, sináptico, molecular) y abordajes multitécnicos. Nos propusimos analizar in vitro una red neural de la unión mesopontina del tronco encefálico críticamente implicada en el control del sueño de movimientos oculares rápidos (S-REM). Pese al cúmulo de evidencias que apoyan el papel desempeñado por esta red en relación al S-REM, los mecanismos celulares y sinápticos que subyacen a este control son poco conocidos y continúan siendo objeto de intensa investigación. Para avanzar en el conocimiento de estos mecanismos, se llevó a cabo la caracterización morfológica y funcional de una rodaja de tronco encefálico de la rata, en la que las estructuras críticas para el control del S-REM, i.e.: núcleos tegmentales laterodorsal y pedúnculopontino, y su proyección al núcleo reticular pontis oralis (PnO), están presentes y son operativas. La inclusión del núcleo motor del trigémino en la rodaja permitió detectar cambios de la excitabilidad de las motoneuronas ante manipulaciones farmacológicas del PnO, representativos de los cambios del tono muscular asociados a maniobras similares realizadas in vivo. La utilización de este modelo in vitro de S-REM, permitirá aportar a la dilucidación de las estrategias neurales que operan en niveles intermedios de organización del SN en mamíferos para la generación y regulación de un estado comportamental.

The study of the neural basis of behavior is a major challenge in Neuroscience. Advancing our knowledge in this field depends, critically, on the use of experimental paradigms that provide multiple levels of analysis, as well as powerful techniques. We have selected, as a model of a neural plan that organizes a complex behavior, a neural network located in the mesopontine junction. This region is thought to be both necessary and sufficient for the generation of rapid eye movement (REM) sleep, although the cellular and synaptic mechanisms involved in the control of this behavioral state at the mesopontine level are still under debate and remain poorly understood. As part of a long term effort to gain insight into these mechanisms, we carried out the morphological and functional characterization of a slice preparation of rat brainstem and we demonstrate that critical structures for the control of REM sleep - the laterodorsal and pedunculopontine tegmental nuclei and their projection to the oral part of the pontine reticular nucleus (PnO) - are present and are operational. The presence of the trigeminal motor nucleus in the slice sought to include in the experimental model a structure capable of expressing changes of the excitability of the motorneurons caused by pharmacological manipulations of the PnO, representative of changes of muscle tone associated with similar maneuvers performed in vivo. The use of this in vitro model of REM sleep will provide critical information to elucidate neural strategies that operate at intermediate levels of central nervous system organization in mammals to control behavioral states.

O estudo de estratégias neurais para a organização do comportamento em vertebrados constitui um desafio maior para a Neurociencia. O avanço do conhecimento nessa área depende criticamente da utilização de modelos experimentais adequados que suportem múltiplos níveis de análise (por exemplo: comportamental, circuital, celular, sináptico e molecular) e abordagens por múltiplas técnicas. Decidiu-se analisar in vitro uma rede neural da união mesopontina do tronco encefálico criticamente envolvida no controle do sono de movimentos oculares rápidos (S-REM). Apesar da riqueza de provas que sustentam o papel desta rede em relação ao S-REM, os mecanismos celulares e sinápticos subjacentes a este controle são pouco conhecidos e permanecem sob intensa investigação. Para avançar no conhecimento desses mecanismos, caracterizou-se morfológica e funcionalmente uma fatia de tronco encefálico de rato, na qual as estruturas críticas para o controle do S-REM, i.e.: núcleos tegmentais laterodorsal e pedunculopontino, e sua projeção para o núcleo reticular pontis oralis (PnO) estão presentes e operantes. A inclusão do núcleo motor do trigêmeo na fatia permitiu detectar mudanças da excitabilidade das motoneuronas provocadas por manipulações farmacológicas do PnO, representativas das alterações do tônus muscular associados com operações semelhantes quando realizados in vivo. A utlização deste modelo in vitro de S-REM permitirá contribuir para a elucidação de estratégias neurais que operam em níveis intermedios de organização do SN de mamíferos para a geração e regulação de um estado comportamental.

Avances en el desarrollo infantil temprano: desde neuronas hasta programas a gran escala / Advances in early childhood development: from neurons to big scale programs

Resumen: El desarrollo infantil temprano (DIT) es la base del desarrollo económico y social de los países y de su capacidad de cumplir con los Objetivos de Desarrollo Sostenible (ODS). La gestación y los primeros 3 años de vida son fundamentales para que los niños tengan un desarrollo físico, psicosocial, emocional y cognitivo adecuado para el resto de sus vidas. La crianza y el cuidado cariñoso y sensible a las necesidades de los niños durante la gestación y la primera infancia son esenciales para el desarrollo de los billones de neuronas y trillones de sinapsis necesarias. El DIT requiere de acceso a buena nutrición y servicios de salud desde la gestación, crianza sensible de acuerdo a la etapa de desarrollo del niño, protección social y del bienestar del niño, y oportunidades de estimulación y aprendizaje temprano. Para mejorar el DIT a nivel nacional se recomiendan seis acciones con fuerte participación de la sociedad civil: expandir la voluntad política y financiamiento, crear un entorno de políticas favorables basadas en evidencia, construir capacidad con coordinación intersectorial, asegurar una gobernanza justa y transparente de los programas y servicios, aumentar apoyo a la investigación multidisciplinaria y promover el desarrollo de líderes. México ha logrado avances importantes en DIT bajo el liderazgo del Sector Salud, pero enfrenta retos significativos para implementar estas recomendaciones. La reciente creación de un marco nacional intersectorial favorable al DIT con apoyo de los organismos internacionales y la participación de la sociedad civil pueden ayudar a sobreponer estos retos.

Abstract: Early childhood development (ECD) is the basis of countries' economic and social development and their ability to meet the Sustainable Development Goals (SDGs). Gestation and the first three years of life are critical for children to have adequate physical, psychosocial, emotional and cognitive development for the rest of their lives. Nurturing care and protection of children during gestation and early childhood are necessary for the development of trillions of neurons and trillions of synapses necessary for development. ECD requires access to good nutrition and health services from gestation, responsive caregiving according to the child's developmental stage, social protection and child welfare, and early stimulation and learning opportunities. Six actions are recommended to improve national ECD programs: expand political will and funding; create a supportive, evidence-based policy environment; build capacity through intersectoral coordination; ensure fair and transparent governance of programs and services; increase support for multidisciplinary research; and promote the development of leaders. Mexico has made significant progress under the leadership of the Health Ministry, but still faces significant challenges. The recent creation of a national intersectoral framework to enable ECD with support of international organizations and the participation of civil society organizations can help overcome these challenges.

Are astrocytes executive cells within the central nervous system? / ¿Son los astrocitos células ejecutivas dentro del Sistema Nervioso Central?

ABSTRACT Experimental evidence suggests that astrocytes play a crucial role in the physiology of the central nervous system (CNS) by modulating synaptic activity and plasticity. Based on what is currently known we postulate that astrocytes are fundamental, along with neurons, for the information processing that takes place within the CNS. On the other hand, experimental findings and human observations signal that some of the primary degenerative diseases of the CNS, like frontotemporal dementia, Parkinson’s disease, Alzheimer’s dementia, Huntington’s dementia, primary cerebellar ataxias and amyotrophic lateral sclerosis, all of which affect the human species exclusively, may be due to astroglial dysfunction. This hypothesis is supported by observations that demonstrated that the killing of neurons by non-neural cells plays a major role in the pathogenesis of those diseases, at both their onset and their progression. Furthermore, recent findings suggest that astrocytes might be involved in the pathogenesis of some psychiatric disorders as well.

RESUMEN Evidencias experimentales sugieren que los astrocitos desempeñan un rol crucial en la fisiología del sistema nervioso central (SNC) modulando la actividad y plasticidad sináptica. En base a lo actualmente conocido creemos que los astrocitos participan, en pie de igualdad con las neuronas, en los procesos de información del SNC. Además, observaciones experimentales y humanas encontraron que algunas de las enfermedades degenerativas primarias del SNC: la demencia fronto-temporal; las enfermedades de Parkinson, de Alzheimer, y de Huntington, las ataxias cerebelosas primarias y la esclerosis lateral amiotrófica, que afectan solo a los humanos, pueden deberse a astroglíopatía. Esta hipótesis se sustenta en hallazgos que demostraron que la muerte neuronal que en ellas ocurre es debida al compromiso de células no-neuronales que juegan rol principal en su iniciación y desarrollo. Más aún, observaciones recientes señalan que los astrocitos podrían estar implicados en la patogenia de algunas enfermedades psiquiátricas.

Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

The timing and mechanisms of protection by hyperbaric oxygenation (HBO) in hypoxic-ischemic brain damage (HIBD) have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders) were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI) and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm) occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.

Cortical spreading depression in migraine-time to reconsider? / Depressão alastrante cortical na enxaqueca – hora de reconsiderar?

New evidence concerning the pathophysiology of migraine has come from the results of therapeutic transcranial magnetic stimulation (tTMS). The instantaneous responses to single pulses applied during the aura or headache phase, together with a number of other observations, make it unlikely that cortical spreading depression is involved in migraine. tTMS is considered to act by abolishing abnormal impulse activity in cortical pyramidal neurons and a suggestion is made as to how this activity could arise.

Novas evidências referentes à fisiopatologia da enxaqueca são o resultado de estimulação magnética transcraniana terapêutica (tTMS). As respostas imediatas a pulsos simples aplicados durante as fases de aura ou de cefaleia, em associação a diversas outras observações, tornam improvável a ideia de que a depressão alastrante esteja envolvida na enxaqueca. Considera-se que tTMS tenha sua ação abolindo atividade anormal de impulsos em neurônios corticais piramidais, sugerindo que esta atividade tenha um papel desencadeante.

Vulnerabilidade de famílias de idosos assistidos pela Estratégia Saúde da Família / Vulnerabilidad de las familias de adultos mayores asistidas por la Estrategia Salud de la Familia / Vulnerability of families of elderly citizens cared for by the Family Health Strategy

RESUMO Objetivo: estudo descritivo, exploratório, de corte transversal, cujo objetivo foi identificar a vulnerabilidade de famílias de idosos assistidos pela Estratégia Saúde da Família (ESF). Método: foi desenvolvido por meio de entrevistas domiciliárias realizadas com uma amostra de 500 famílias de idosos assistidas por 32 equipes da ESF da cidade de Dourados, MS. O Índice de Desenvolvimento da Família (IDF) foi adaptado para classificá-las em função da situação de vulnerabilidade. Resultados: os resultados revelaram a presença de famílias multigeracionais, com baixa escolaridade entre os indivíduos com idade superior a 20 anos e alta taxa de analfabetismo entre os idosos. Identificaram-se 403 famílias em situação de vulnerabilidade aceitável, 95 em vulnerabilidade grave e duas famílias em situação de vulnerabilidade muito grave. As dimensões mais críticas do IDF foram os acessos ao conhecimento e ao trabalho. Conclusão: conclui-se que há necessidade de mais investimentos no cuidado a esses idosos e suas famílias na Atenção Básica. .

RESUMEN Objetivo: estudio descriptivo, exploratorio, transversal, con el objetivo de identificar la vulnerabilidad de familias adultos mayores asistidas por la Estrategia Salud de la Familia (ESF). Método: fue desarrollado mediante entrevistas a una muestra de 500 familias de adultos mayores bajo la responsabilidad de 32 equipos de ESF en la ciudad de Dourados, MS, Brasil. El Índice de Desarrollo de la Familia (IDF) fue adaptado para clasificar las familias de acuerdo a la situación de vulnerabilidad. Resultados: los resultados revelaron la presencia de familias multigeneracionales con bajo nivel de educación entre las personas mayores de 20 años y las altas tasas de analfabetismo entre los adultos mayores. Se identificaron 403 familias en situación de vulnerabilidad aceptable, 95 con vulnerabilidad grave y dos familias en situación de vulnerabilidad muy grave. Las dimensiones más críticas en el IDF fueron el acceso al conocimiento y al trabajo. Conclusión: se concluye que existe la necesidad de una mayor inversión, con un enfoque en la atención primaria, con el fin de atender a las personas mayores y sus familias. .

ABSTRACT Objective: the present descriptive, exploratory, cross-sectional study aimed to identify the vulnerability of families of elderly citizens cared for by the Family Health Strategy (FHS). Method: the research employed home interviews and was developed with a sample of 500 families of aged people cared for by 32 FHS teams in the city of Dourados, MS, Brazil. The Family Development Index (FDI) was adapted in order to classify the families according to their degree of vulnerability. Results: the results revealed the presence of multigenerational families with low educational levels among individuals over the age of 20 and high illiteracy rates among elderly citizens. There were 403 families whose vulnerability was acceptable, 95 in severe vulnerability, and two families in a condition of very severe vulnerability. The most critical dimensions of the FDI were the access to knowledge and to work. Conclusion: the study identifi ed that there is still a need for further investments that can assist these aged people and their families in the Primary Health Care. .

Estado nutricional de vitaminas A e D em crianças participantes de programa de suplementação alimentar / Vitamin A and D status among child participants in a food supplementation program / Concentraciones séricas de vitaminas A y D en niños del programa de distribución de leche fortificada

Foram avaliados as concentrações séricas de vitaminas A e D e os fatores associados em crianças beneficiárias de programa de distribuição de leite fortificado, sendo utilizados modelos de regressão linear múltiplos com seleção hierárquica de variáveis independentes (condição sociodemográfica, de saúde, alimentação, amamentação, consumo do leite fortificado, exposição solar, antropometria, retinol e calcidiol séricos). Foram consideradas insuficiência e deficiência de vitamina A e de vitamina D as concentrações séricas < 1,05µmol/L, 0,70µmo/L, 30ng/mL e 20ng/mL, respectivamente. Houve inadequação do consumo alimentar de vitaminas A e D. As prevalências de insuficiência e deficiência de vitamina A e de vitamina D foram 19%, 6%, 82% e 58%, respectivamente. Os fatores associados às menores concentrações séricas de vitamina A foram: amamentação materna exclusiva < 120 dias, ausência de trabalho materno combinada com menor escolaridade materna, maior número de pessoas que consomem leite fortificado no domicílio e menor vitamina D sérica. Para a vitamina D, foram: menor exposição ao sol e menor vitamina A sérica. Ações de educação nutricional são necessárias para melhorar a situação nutricional dessas crianças.

Vitamin A and D serum concentrations and risk factors for their deficiencies were investigated in children participating in a government-sponsored fortified milk program. The study used multivariate linear regression analysis with hierarchical selection of independent variables: socio-demographic conditions, children's health, food consumption, breastfeeding, fortified milk, exposure to sunlight, anthropometric measurements, and serum concentration of retinol and 25(OH)D. Vitamin A and vitamin D insufficiency and deficiency values were defined as < 1.05µmol/L, < 0.7µmol/L, < 30ng/mL, and < 20ng/mL, respectively. Vitamin A and D intake was inadequate. Prevalence rates for vitamin A and vitamin D insufficiency and deficiency were 19%, 6%, 82%, and 58%, respectively. Factors associated with low serum vitamin A were exclusive breastfeeding for less than 120 days, low maternal schooling, maternal unemployment, more consumers of fortified milk in the family, and low serum vitamin D. Factors associated with vitamin D deficiency were low exposure to sunlight and low serum vitamin A. Nutritional education is needed to improve children's nutritional status.

Se evaluaron las concentraciones séricas de vitaminas A y D y factores asociados en niños que se benefician del programa de distribución de leche fortificada. Se utilizaron múltiples modelos de regresión lineal, con una selección jerárquica de las variables independientes (estatus sociodemográfico, salud, alimentación, lactancia materna, consumo de leche fortificada, exposición al sol, medidas antropométricas, retinol y calcidiol séricos). Para la insuficiencia y deficiencia de vitamina A y vitamina D, se adoptaron concentraciones séricas < 1,05µmol/L, < 0,70µmol/L, < 30ng/mL, < 20ng/mL, respectivamente. La inadecuación del consumo de alimentos para vitamina A y vitamina D fue de un 40% y 100%, respectivamente. La prevalencia de insuficiencia y la deficiencia de vitamina A y vitamina D fue de un 19%, 6%, 82% y 58%, respectivamente. Los factores asociados más pequeños de vitamina A sérica fueron: lactancia exclusiva < 120 días, ausencia de empleo de la madre, combinada con una baja educación materna y menor vitamina D sérica. Para la vitamina D fueron: menor exposición al sol y menor vitamina A sérica. Las acciones de educación nutricional son necesarias para mejorar la situación nutricional de estos niños.

Perioperative myocardial infarction in patients undergoing myocardial revascularization surgery / Infarto do miocárdio perioperatório em pacientes submetidos à cirurgia de revascularização miocárdica

Introduction: Perioperative myocardial infarction adversely affects the prognosis of patients undergoing coronary artery bypass graft and its diagnosis was hampered by numerous difficulties, because the pathophysiology is different from the traditional instability atherosclerotic and the clinical difficulty to be characterized. Objective: To identify the frequency of perioperative myocardial infarction and its outcome in patients undergoing coronary artery bypass graft. Methods: Retrospective cohort study performed in a tertiary hospital specialized in cardiology, from May 01, 2011 to April 30, 2012, which included all records containing coronary artery bypass graft records. To confirm the diagnosis of perioperative myocardial infarction criteria, the Third Universal Definition of Myocardial Infarction was used. Results: We analyzed 116 cases. Perioperative myocardial infarction was diagnosed in 28 patients (24.1%). Number of grafts and use and cardiopulmonary bypass time were associated with this diagnosis and the mean age was significantly higher in this group. The diagnostic criteria elevated troponin I, which was positive in 99.1% of cases regardless of diagnosis of perioperative myocardial infarction. No significant difference was found between length of hospital stay and intensive care unit in patients with and without this complication, however patients with perioperative myocardial infarction progressed with worse left ventricular function and more death cases. Conclusion: The frequency of perioperative myocardial infarction found in this study was considered high and as a consequence the same observed average higher troponin I, more cases of worsening left ventricular function and death. .

Introdução: O infarto do miocárdio perioperatório afeta negativamente o prognóstico dos pacientes submetidos à cirurgia de revascularização do miocárdio e seu diagnóstico esbarra em inúmeras dificuldades, pois a fisiopatologia é diferente da tradicional instabilidade aterosclerótica e o quadro clínico de difícil caracterização. Objetivo: Identificar a frequência de infarto do miocárdio perioperatório e seu desfecho em pacientes submetidos à cirurgia de revascularização do miocárdio. Métodos: Coorte retrospectiva realizada em hospital terciário especializado em cardiologia, de 1 de maio de 2011 a 30 de abril de 2012, que incluiu todos os prontuários contendo registros de cirurgia de revascularização do miocárdio. Para confirmação diagnóstica do infarto do miocárdio perioperatório, foram utilizados os critérios da Third Universal Definition of Myocardial Infarction Resultados: Foram analisados 116 casos. Foi diagnosticado infarto do miocárdio perioperatório em 28 pacientes (24,1%). Número de enxertos e utilização e tempo de circulação extracorpórea foram fatores associados a este diagnóstico e a média de idade foi significativamente mais elevada neste grupo. O critério diagnóstico elevação de troponina I foi positivo em 99,1% dos casos, independentemente do diagnóstico de infarto do miocárdio perioperatório. Não foi encontrada diferença significativa entre tempo de internação hospitalar e em unidade de terapia intensiva nos grupos com e sem esta complicação, porém pacientes com infarto do miocárdio perioperatório evoluíram com pior função ventricular esquerda e mais casos de óbito. Conclusão: A frequência de infarto do miocárdio perioperatório encontrada neste trabalho foi considerada alta e como consequência do mesmo observou-se média mais elevada de troponina I, mais casos de piora da função ventricular esquerda e óbito. .

Tuberculosis in renal transplant patients: The experience of a single center in Medellín-Colombia, 2005-2013 / Tuberculose em pacientes transplantados renais: experiência de um único centro em Medellín-Colômbia, 2005-2013

Introduction: Tuberculosis is a common opportunistic infection in renal transplant patients. Objective: To obtain a clinical and laboratory description of transplant patients diagnosed with tuberculosis and their response to treatment during a period ranging from 2005 to 2013 at the Pablo Tobón Uribe Hospital. Methods: Retrospective and descriptive study. Results: In 641 renal transplants, tuberculosis was confirmed in 12 cases. Of these, 25% had a history of acute rejection, and 50% had creatinine levels greater than 1.5 mg/dl prior to infection. The disease typically presented as pulmonary (50%) and disseminated (33.3%). The first phase of treatment consisted of 3 months of HZRE (isoniazid, pyrazinamide, rifampicin and ethambutol) in 75% of the cases and HZME (isoniazid, pyrazinamide, moxifloxacin and ethambutol) in 25% of the cases. During the second phase of the treatment, 75% of the cases received isoniazid and rifampicin, and 25% of the cases received isoniazid and ethambutol. The length of treatment varied between 6 and 18 months. In 41.7% of patients, hepatotoxicity was associated with the beginning of anti-tuberculosis therapy. During a year-long follow-up, renal function remained stable, and the mortality rate was 16.7%. Conclusion: Tuberculosis in the renal transplant population studied caused diverse nonspecific symptoms. Pulmonary and disseminated tuberculosis were the most frequent forms and required prolonged treatment. Antituberculosis medications had a high toxicity and mortality. This infection must be considered when patients present with a febrile syndrome of unknown origin, especially during the first year after renal transplant. .

Introdução: A tuberculose é uma infecção oportunista comum em pacientes transplantados renais. Objetivo: Oferecer uma descrição clínica e laboratorial de pacientes transplantados com diagnóstico de tuberculose e sua resposta ao tratamento durante o período entre 2005 e 2013 no Hospital Pablo Tobón Uribe. Métodos: Estudo retrospectivo descritivo. Resultados: Em 641 transplantes renais, a tuberculose foi confirmada em 12 pacientes. Destes, 25% tinham histórico de rejeição aguda e 50% apresentaram níveis de creatinina superiores a 1,5 mg/dl antes da infecção. A patologia geralmente se apresentava como pulmonar (50%) e disseminada (33,3%). A primeira fase do tratamento consistiu de três meses de HZRE (isoniazida, pirazinamida, rifampicina e etambutol) em 75% dos casos e HZME (isoniazida, pirazinamida, moxifloxacina e etambutol) em 25% dos pacientes. Durante a segunda fase do tratamento, 75% dos pacientes receberam isoniazida e rifampicina e 25% isoniazida e etambutol. A duração do tratamento variou entre seis e 18 meses. Em 41,7% dos pacientes, hepatotoxicidade foi associada ao início do tratamento da tuberculose. Durante o seguimento de um ano a função renal manteve-se estável e a taxa de mortalidade foi de 16,7%. Conclusão: A tuberculose foi responsável por diversos sintomas inespecíficos na população de transplantados renais estudada. Tuberculose pulmonar e disseminada foram as formas mais frequentes de acometimento e necessitaram de tratamento prolongado. Medicamentos contra a tuberculose apresentaram alta toxicidade e mortalidade. Esta infecção deve ser considerada quando o paciente apresenta síndrome febril de origem desconhecida, especialmente durante o primeiro ano após o transplante renal. .

Infection of the heart of Pimelodus ornatus (Teleostei, Pimelodidae), by Myxobolus sp. (Myxozoa, Myxobolidae) / Infecção do tecido cardíaco de Pimelodus ornatus (Teleostei, Pimelodidae), por Myxobolus sp. (Myxozoa, Myxobolidae)

The phylum Myxozoa Grassé, 1970, consists of a heterogenous group of around 50 genera that are worldwide disseminated in a wide variety of aquatic media. In the present study, 43 specimens of Pimelodus ornatus were collected from an adjacent area to the Cachoeira do Arari municipality on Marajó Island, in the Brazilian state of Pará, in 2013. Macroscopic analysis showed the presence of whitened plasmodia located in the cardiac muscle and also in the region between the bulbus arteriosus and atrium cordis. Microscopic analysis on the parasitized tissues revealed spores that were typically piriform, with the anterior portion slightly narrower than the posterior end. The spore valves were symmetrical. The present species is placed in the genus Myxobolus Butschli, 1882, because of the presence of a pair of equal polar capsules in each spore. The prevalence of parasitism observed was 13.9% (6/43). This research note reports the first occurrence of Myxobolus as a parasite of the heart in the teleostean fish P. ornatus in the Amazon region and confirms the occurrence of secondary myocarditis in this fish, caused by parasitism by Myxobolus sp. The rarity of this parasitic species of Myxobolus at this tissue site, associated with other spore morphology characteristics in the fish, suggests that it is an undescribed species.

O filo Myxozoa Grassé, 1970, consiste em um grupo heterogêneo de cerca de 50 gêneros que são disseminados em todo o mundo em uma grande variedade de meios aquáticos. No presente estudo, quarenta e três espécimes de Pimelodus ornatus foram coletados a partir de uma área adjacente à cidade de Cachoeira do Arari, na Ilha do Marajó, no Estado do Pará, em 2013. À análise macroscópica verificou-se a presença de plasmódios esbranquiçados, localizados no músculo cardíaco e também na região entre o bulbus arteriosus e o atrium cordis. A análise microscópica dos tecidos parasitados revelou esporos que eram tipicamente piriformes, com a porção anterior um pouco mais estreita do que a extremidade posterior, sendo suas válvulas simétricas. A prevalência do parasitismo observada foi de 13,9% (6/43). Esta nota de pesquisa relata a primeira ocorrência de Myxobolus como um parasita do coração no peixe teleósteo P. ornatus, na Região Amazônica e, confirma a ocorrência de miocardite secundária causada por esse parasitismo. A raridade da ocorrência de Myxobolus sp. neste tecido, associado a outras características morfológicas dos esporos no peixe, sugere que é uma espécie não descrita.