Melatonin attenuates developmental deficits and prevents hippocampal injuries in male and female rats subjected to neonatal anoxia.

Hypoxia in preterm infants is a clinical condition that has been associated with cognitive and behavioral disturbances for which treatment strategies are strongly required. Melatonin administration following brain insults has been considered a promising therapeutic strategy due to its antioxidant and anti-inflammatory effects. Not surprisingly, it has been extensively studied for preventing disturbances following brain injury. This study evaluated the effects of melatonin on developmental disturbances, memory disruption, and hippocampal cell loss induced by neonatal anoxia in rats. Neonatal Wistar rats were subjected to anoxia and subsequently treated with melatonin. Later, maturation of physical characteristics, ontogeny of reflexes, learning and memory in the Morris water maze (MWM), and estimates of the number of hippocampal neurons, were evaluated. Melatonin treatment attenuated (1) female anoxia-induced delay in superior incisor eruption, (2) female anoxia-induced vibrissae placement reflexes, and (3) male and female anoxia-induced hippocampal neuronal loss. Melatonin also promoted an increase (5) in swimming speeds in the MWM. In addition, PCA analysis showed positive associations between the acoustic startle, auditory canal open, and free fall righting parameters and negative associations between the male vehicle anoxia group and the male melatonin anoxia group. Therefore, melatonin treatment attenuates both anoxia-induced developmental deficits and hippocampal neuronal loss.

Post-weaning social isolation modifies neonatal anoxia-induced changes in energy metabolism and growth of rats.

Neonatal oxygen deficiency in rats may disturb growth and long-term metabolic homeostasis. In order to facilitate metabolic evaluation, the subjects are usually housed individually. However, social isolation associated with individually housed conditions alters animal behavior, which may influence the experimental results. This study investigated the effects of social isolation on neonatal anoxia-induced changes in growth and energy metabolism. Male and female Wistar rats were exposed, on postnatal day 2 (P2), to either 25-min of anoxia or control treatment. From P27 onward, part of the subjects of each group was isolated in standard cages, and the remaining subjects were housed in groups. At P34 or P95, the subjects were fasted for 18 h, refeed for 1 h, and then perfused 30 min later. Glycemia, leptin, insulin, and morphology of the pancreas were evaluated at both ages. For subjects perfused at P95, body weight and food intake were recorded up to P90, and the brain was collected for Fos and NeuN immunohistochemistry. Results showed that male rats exposed to neonatal anoxia and social isolation exhibited increased body weight gain despite the lack of changes in food intake. In addition, social isolation (1) decreased post-fasting weight loss and post-fasting food intake and (2) increased glycemia, insulin, and leptin levels of male and female rats exposed to anoxia and control treatments, both at P35 and P95. Furthermore, although at P35, anoxia increased insulin levels of males, it decreased the area of the ß-positive cells in the pancreas of females. At P95, anoxia increased post-prandial weight loss of males, post-fasting food intake, insulin, and leptin, and decreased Fos expression in the arcuate nucleus (ARC) of males and females. Hyperphagia was associated with possible resistance to leptin and insulin, suspected by the high circulating levels of these hormones and poor neuronal activation of ARC. This study demonstrated that continuous social isolation from weaning modifies, in a differentiated way, the long-term energy metabolism and growth of male and female Wistar rats exposed to neonatal anoxia or even control treatments. Therefore, social isolation should be considered as a factor that negatively influences experimental results and the outcomes of the neonatal injury. These results should also be taken into account in clinical procedures, since the used model simulates the preterm babies' conditions and some therapeutic approaches require isolation.

Pathophysiological aspects of neonatal anoxia and temporal expression of S100ß in different brain regions.

The aim of this study was to investigate the temporal variations of S100ß in the hippocampus, cerebellum and cerebral cortex of neonatal rats (Wistar strain) under anoxic conditions. Real-time PCR and western blotting techniques were used for gene expression and protein analysis. Animals were divided into two groups, a control group and an anoxic group, and further separated at different time points for analysis. After anoxia, S100ß gene expression showed a significant peak in the hippocampus and cerebellum after 2 h, followed by a decline compared to the control group at other time points. The increased gene expression in these regions was also accompanied by an increase in S100ß protein levels in the anoxia group, observable 4 h after injury. In contrast, S100ß mRNA content in the cerebral cortex never exceeded control values at any time point. Similarly, the protein content of S100ß in the cerebral cortex did not show statistically significant differences compared to control animals at any assessment time point. These results suggest that the production profile of S100ß differs by brain region and developmental stage. The observed differences in vulnerability between the hippocampus, cerebellum and cerebral cortex may be attributed to their distinct developmental periods. The hippocampus and cerebellum, which develop earlier than the cerebral cortex, showed more pronounced effects in response to anoxia, which is supported by the gene expression and protein content in this study. This result reveals the brain region-dependent nature of S100ß as a biomarker of brain injury.

Sensorimotor development of male and female rats subjected to neonatal anoxia.

Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the most important reasons for morbidity and mortality in term-born infants. HIE impacts early somatic, neurological, and motor development including social. To illustrate the damages in the sensorimotor system, an adapted and validated model of neonatal anoxia is used. This study evaluated the sex differences in Wistar rats, neurological reflex, and motor development at the suckling period. Short- and long-term impairments associated with sex differences were observed. In general, anoxic males were more affected in comparison to their control group and to anoxic females. Long-lasting effects of the injury in adolescent rats predominately affected males. Similar to previous studies, we also found a decrease in the number of the substantia nigra cells in both sexes, compared to their control. So far, the results indicate that HIE caused neurobehavioral alterations and asymmetrical motor behavior with brain damage, possibly related to cognitive impairments previously observed at adolescence. These alterations may represent a useful endpoint for studying the efficacy of potential strategies that may improve the developmental consequences of a perinatal asphyxia insult in humans.

Neonatal Anoxia Impacts Rats' Maternal Behavior and Offspring Development due to Ultrasonic Vocalization's Impairment.

Hypoxic-ischemic encephalopathy is a severe clinical condition, among others, affecting the brain after offspring exposure to neonatal anoxia, which causes persistent sensorimotor and cognitive deficits. During peripartum, maternal behaviors are crucial for the healthy development of the offspring. In rats, the vocalization of newborns, around 40 kHz, corresponds to separation calls that encourage their mothers to retrieve them. Alterations in this pattern affect the maternal behavior addressed to the offspring. This study aimed to evaluate the maternal behavior of primiparous rats whose offspring were exposed to neonatal anoxia in P2 (postpartum day) during the lactation period, to assess mother-pup interactions through the pups' vocalization from P3 to P18. It also intends to quantify eventual neuronal alterations in the mothers' medial preoptic area after the last weaning (P21) through FOS protein expression. Anoxia offspring were found to reduce maternal behaviors toward them, increased frequency of separation calls in the male anoxia group, and reduced vocalization rate in the female anoxia group compared to their respective controls. Body weight gain reduction of males' and females' anoxia was observed. We concluded that anoxia exerts deleterious effects on the vocalization patterns of the pups, with sex differences that alter maternal behavior toward them. Impaired USV makes an additional negative impact on the already noxious effects of neonatal anoxia. Understanding those phenomena applies/contributes to guiding procedures and strategies to mitigate the deleterious outcomes and orient research concerning the complexity of neonatal anoxia events and the influence of maternal care quality concerning the pups, which should also be considered sex differences.

Neonatal anoxia increases nociceptive response in rats: Sex differences and lumbar spinal cord and insula alterations.

Neonatal anoxia is a well-known world health problem that results in neurodevelopmental deficits, such as sensory alterations that are observed in patients with cerebral palsy and autism disorder, for which oxygen deprivation is a risk factor. Nociceptive response, as part of the sensory system, has been reported as altered in these patients. To determine whether neonatal oxygen deprivation alters nociceptive sensitivity and promotes medium- and long-term inflammatory feedback in the central nervous system, Wistar rats of around 30 h old were submitted to anoxia (100% nitrogen flux for 25 min) and evaluated on PND23 (postpartum day) and PND90. The nociceptive response was assessed by mechanical, thermal, and tactile tests in the early postnatal and adulthood periods. The lumbar spinal cord (SC, L4-L6) motor neurons (MNs) and the posterior insular cortex neurons were counted and compared with their respective controls after anoxia. In addition, we evaluated the possible effect of anoxia on the expression of astrocytes in the SC at adulthood. The results showed increased nociceptive responses in both males and females submitted to anoxia, although these responses were different according to the nociceptive stimulus. A decrease in MNs in adult anoxiated females and an upregulation of GFAP expression in the SC were observed. In the insular cortex, a decrease in the number of cells of anoxiated males was observed in the neonatal period. Our findings suggest that oxygen-deprived nervous systems in rats may affect their response at the sensorimotor pathways and respective controlling centers with sex differences, which were related to the used stimulus.

Impact of neonatal anoxia and hypothermic treatment on development and memory of rats.

Therapeutic hypothermia (TH) is well established as a standard treatment for term and near-term infants. However, therapeutic effects of hypothermia following neonatal anoxia in very premature babies remains inconclusive. The present rodent model of preterm neonatal anoxia has been shown to alter developmental milestones and hippocampal neurogenesis, and to disrupt spatial learning and memory in adulthood. These effects seem to be reduced by post-insult hypothermia. Epigenetic-related mechanisms have been postulated as valuable tools for developing new therapies. Dentate gyrus neurogenesis is regulated by epigenetic factors. This study evaluated whether TH effects in a rodent model of preterm oxygen deprivation are based on epigenetic alterations. The effects of TH on both developmental features (somatic growth, maturation of physical characteristics and early neurological reflexes) and performance of behavioral tasks at adulthood (spatial reference and working memory, and fear conditioning) were investigated in association with the possible involvement of the epigenetic operator Enhancer of zeste homolog 2 (Ezh2), possibly related to long-lasting effects on hippocampal neurogenesis. Results showed that TH reduced both anoxia-induced hippocampal neurodegeneration and anoxia-induced impairments on risk assessment behavior, acquisition of spatial memory, and extinction of auditory and contextual fear conditioning. In contrast, TH did not prevent developmental alterations caused by neonatal anoxia and did not restore hippocampal neurogenesis or cause changes in EZH2 levels. In conclusion, despite the beneficial effects of TH in hippocampal neurodegeneration and in reversing disruption of performance of behavioral tasks following oxygen deprivation in prematurity, these effects seem not related to developmental alterations and hippocampal neurogenesis and, apparently, is not caused by Ezh2-mediated epigenetic alteration.

Impairment of nociceptive responses after neonatal anoxia correlates with somatosensory thalamic damage: A study in rats.

Chronic neuropathic pain resulting from damage to the central or peripheral nervous system is a prevalent and debilitating condition affecting 7-18% of the population. Symptoms include spontaneous pain, dysesthesia, paresthesia, allodynia and hyperalgesia. The reported sensory symptoms are comorbid with behavioral disabilities such as insomnia and depression. Neonatal anoxia, a worldwide clinical problem in both neonatal and pediatric care, causes long-term deficits similar to those mentioned. The effect of neonatal anoxia on the maturation of nociceptive pathways has been sparsely explored. To address this question and to determine whether the effects differ depending on sex, a neonatal anoxia model was used in which Wistar rat pups approximately 30 h old and of both sexes were placed in a chamber with 100% nitrogen flow at 3.5 L/min for 25 min at 36 °C ± 1 °C. After recovery, the animals (n = 16 in each group (anoxia and control; males and females)) were returned to their mothers. The control animals were subjected to the same conditions, but no gas exchange was performed. At postnatal day (PND) 18 and PND43, the animals were subjected to pain testing by stimulation of the hind paws with von Frey monofilaments. The results revealed a significant reduction (approximately 50%) in the pain threshold in the animals exposed to anoxia in comparison with their respective controls. The pain threshold increased between PND18 and PND43. A sex-based difference was observed in the male control group at PND18. Histological analysis revealed decreased cell numbers in the ventral posterolateral thalamic nucleus (VPL), with sex differences. These results demonstrate the long-lasting negative impact of neonatal anoxia and indicate the relevance of performing suitable approaches taking in consideration the possible sex differences.

Neonatal anoxia impairs long-term energy metabolism and somatic development of Wistar rats.

BACKGROUND: Neonatal anoxia may cause neurological injuries, behavioral alterations and changes in somatic growth. Somatic developmental changes suggest a possible effect of anoxia on energy metabolism and/or feeding behavior. Short-term effects of oxygen deficit on energy homeostasis have been described. In contrast, just a few studies report long-term effects. This study investigated the effects of neonatal anoxia on energy metabolism and somatic development at adulthood of males and females Wistar rats. METHOD: Male (m) and female (f) rats were exposed, on postnatal day 2 (P2), to either 25-min of Anoxia or Control treatment. At P34 part of the subjects of each group was fasted for 18 h, refeed for 1 h and then perfused 30 min later, at P35; the remaining subjects were submitted to these treatments at P94 and perfused at P95. Therefore, there were 8 groups: AmP35, AmP95, AfP35, AfP95, CmP35, CmP95, CfP35 and CfP95. For subjects perfused at P95, body weight and food intake were recorded up to P90. For subjects perfused at P35 and P95, glycemia, leptin and insulin were assessed after fasting and refeed. After perfusion the encephalon and pancreas were collected for Fos immunohistochemistry and Hematoxylin-Eosin stain analyses. RESULTS: Even though neonatal anoxia did not interfere with regular food intake, it reduced body weight gain along growing in both male and female subjects as compared to the corresponding controls. At P35 neonatal anoxia decreased post-prandial glycemia and increased insulin. While at P95 neonatal anoxia altered the pancreatic histomorphology and increased post-fasting weight loss, decreasing leptin, insulin and glycemia secretion, as well Fos immunoreactivity (IR) in ARC. CONCLUSION: Neonatal anoxia impairs long-term energy metabolism and somatic development in Wistar rats, with differences related to sex and age.

Acupuntura no Ensino Médico da Universidade Federal Fluminense: Desafios e Perspectivas / Acupuncture in Medical Education at Universidade Federal Fluminense: Challenges and Perspectives

RESUMO O ensino da acupuntura vem sendo progressivamente introduzido em cursos médicos no Brasil e no mundo. Na Universidade Federal Fluminense (UFF), em Niterói (RJ), a reforma curricular da Faculdade de Medicina, implementada em 1994, possibilitou a oferta da disciplina optativa Medicina Tradicional Chinesa/Acupuntura a partir de 1995, além da criação, em 1997, de um curso de especialização em acupuntura destinado ao público médico. Este artigo apresenta um estudo que buscou identificar os principais desafios e perspectivas relacionados a esse ensino na graduação e pós-graduação médicas da UFF, resgatando o debate sobre a polarização paradigmática entre a acupuntura da MTC e a acupuntura neurofisiológica. Foi realizada uma pesquisa qualitativa de caráter etnográfico com análise documental, observação dos cenários de sala de aula e entrevistas semiestruturadas com o professor e alunos da disciplina e curso selecionados. De forma complementar, para garantir a triangulação de informações, utilizou-se a técnica do grupo focal com ex-alunos da graduação médica. O tratamento e a interpretação dos dados deste estudo se ancoraram na discussão epistemológica de Thomas Kuhn - o conceito de paradigmas e a questão da incomensurabilidade de ideias. Os resultados desta pesquisa mostraram que, apesar das diferenças paradigmáticas significativas, há interesse e receptividade de estudantes de Medicina e médicos na abordagem integrativa do processo saúde-doença oferecida pela medicina tradicional chinesa/acupuntura. Entre os aspectos positivos levantados, destacam-se a valorização da abordagem de dimensões do adoecimento humano negligenciadas pela biomedicina, o favorecimento da construção de um olhar integral sobre o sujeito e os bons resultados obtidos nos tratamentos com acupuntura. Os principais desafios apontados foram a necessidade de promover maior integração teórico-prática nas aulas, sugerida pelos alunos da graduação, e a crítica ao reducionismo no ensino da MTC/acupuntura, com simplificação exagerada de conteúdos complexos, feita pelos alunos da pós-graduação. Duas conclusões se destacaram neste estudo. Constatou-se um duplo padrão de aprendizado: abertura dos estudantes de graduação e pós-graduação médicas para o paradigma da medicina chinesa devido às suas especificidades e múltiplas abordagens terapêuticas, ao mesmo tempo em que se buscavam aproximações com o modelo biomédico. A complementaridade entre o paradigma da medicina chinesa e o das neurociências foi a principal característica do processo de incorporação da acupuntura ao ensino médico da UFF.

ABSTRACT The teaching of acupuncture has gradually been introduced into medical courses in Brazil and worldwide. At Universidade Federal Fluminense (UFF), in Niterói, Rio de Janeiro, the newly reformulated medical course curriculum, introduced in 1994, included the offer of an optative discipline in Traditional Chinese Medicine/Acupuncture to start the following year, and also the creation, in 1997, of a specialization course in Acupuncture for qualified medical doctors. In this article, we present a study that aims to identify major challenges and perspectives in Chinese Medicine teaching for undergraduate and graduate students at the UFF medical school, emphasizing the paradigmatic polarization between Traditional Chinese Medicine (TCM) and Neurophysiological Acupuncture. We performed a qualitative, ethnographic study involving document analysis, observation of classroom scenarios, and semi-structured interviews with the teacher and students of the selected discipline and course. In order to ensure triangulation of information, we also used the focus group technique, with former undergraduate students. The data treatment and interpretation of this study were anchored in the epistemological discussion of Thomas Kuhn - the concept of paradigms and the incommensurability of scientific theories. The results of this study show that despite the significant paradigmatic differences, medical students and doctors demonstrate interest in and receptivity towards the integrative approach of health-disease processes offered by traditional TCM. The following positive aspects were highlighted: the valorization of dimensions of human sickness hitherto neglected by biomedicine, the building of an integral perspective on the subject, and the good results obtained with acupuncture. The graduate students noted the need to increase integration between theory and practice, and criticized the reductionism in TCM teaching, with the excessive simplification of complex subjects. Two conclusions can be drawn from this study. A double learning pattern was observed: the interest among undergraduate and graduate students in Traditional Chinese Medicine paradigm, due to its specificities and multiple therapeutic approaches and, at the same time, a search for comparisons with the biomedical model. The complementarity between the paradigms of Traditional Chinese Medicine and neurosciences was the most important characteristic of the introduction of teaching on acupuncture at UFF.

Behavioral, cognitive and histological changes following neonatal anoxia: Male and female rats' differences at adolescent age.

Neonatal anoxia induces long-term brain injury that may underlie neurobehavioral deficits at adolescence. Neonatal anoxia, induced by exposure of 30-hour old pups to 100% nitrogen, represents a non-invasive and global stimulus, which simulates clinical conditions of human pre-term babies (around 6 gestational months). Previous studies showed that neonatal anoxia induced impairments of spatial memory and altered anxiety-like behaviors in male rats tested at adult age. This study evaluated if neonatal anoxia induces similar behavioral effects in female rats, as compared to males, by testing the animals at adolescence, and also searched for possible cell losses in hippocampal subfields. Results in the Elevated Plus Maze test showed that anoxic females spent proportionally more time within the open arms as compared to anoxic males, suggesting a less anxious-like behavior. In the Morris Water Maze Test, latencies and path lengths of the anoxic subjects were longer as compared to control subjects, thus indicating that anoxia disrupted the cognitive functions required for spatial mapping. In addition, results showed that anoxia-induced disruption was greater in male rats as compared to female rats. Stereological analysis revealed that anoxic male rats exhibited significant cell losses in the dorsal hippocampus dentate gyrus and CA1 subfields, but not in CA3-2 subfield. Similar results were observed in the ventral hippocampus, but now with cell loss in the male CA3-2 subfield. There were also significant cell loss differences of anoxic male rats as compared to anoxic female rats. In conclusion, neonatal anoxia induces deleterious and long lasting behavioral and cognitive disruptions, and these effects were stronger in male rats as compared to female rats. These changes are congruent with the pattern of cell losses observed in hippocampal subfields. Together, these results emphasize the relevance of scientific research, aiming at clinical strategies and treatments, consider the sex differential patterns of response to neonatal injury.

Sex differences in somatic and sensory motor development after neonatal anoxia in Wistar rats.

Currently, one of the important causes of brain injury in new-borns is the neonatal anoxia which impacts the perinatology services worldwide. Animal models of anoxia have been used to assess its effects at cellular and behavioural levels in all ages, but few studies focus on sex differences. This study aimed to investigate some physical parameters of development, sensorimotor alterations, early neurological reflexes as well as the density of cells in motor and sensorimotor cerebral cortex of adolescent rats submitted to neonatal anoxia. The results presented significant differences in most of the evaluated parameters, such as body weight and lenght, medio-lateral head axis, eruption of superior incisor, palmar grasp, auditory startle, negative geotaxis, showing that neonatal anoxia affects physical parameters and neurological development, with sex differences. Cellular analysis revealed decreased amount of neurons in motor cortex and primary sensory hind limb and forelimb regions in anoxic group, along with gender difference, as compared to control groups. There is an important rationale for performing early assessment of sensorimotor deficits as there is similarity of the model with high risk human neonates and the sequelae in later life periods, which can be inferred from the present results with suggestion of a possible correlation between sensorimotor development delay and cellular changes in sensorimotor cortex. Furthermore, these observed sex dependent alterations certainly will address further studies and should be considered especially in treatments and strategies to avoid or minimize the neonatal anoxic effects.

Entre neurônios e sinapses: as contribuições de Cajal e Athias para a medicina ibérica entre os séculos XIX e XX / Between neurons and synapses: the contributions of Cajal and Athias to Iberian medicine between the nineteenth and twentieth centuries

Resumo O presente estudo reflete sobre o trajeto da histologia na transição do século XIX para o XX, em Portugal e em Espanha, para estabelecer um paralelo entre as contribuições de Santiago Ramón y Cajal e Marck Athias, ambos determinantes para o desenvolvimento da medicina experimental na Península Ibérica, reconhecidos como pilares de uma nova mentalidade científica europeia, na alvorada do século XX. Neste estudo de caso, refletimos sobre as vicissitudes da construção da ciência na “periferia” europeia, no contexto da categoria historiográfica centro-periferia desenvolvida pelo grupo Science and Technology in the European Periphery (Step), confrontando a realidade ibérica com o modelo de ciência alemã, no período em estudo.

Abstract The trajectory of histology at the cusp of the twentieth century in Portugal and Spain is investigated to draw a parallel between the contributions of Santiago Ramón y Cajal and Marck Athias, both of whom were instrumental in the development of experimental medicine in the Iberian Peninsula and recognized as pillars of a new European scientific mindset at the dawn of the twentieth century. In this case study we reflect on the vicissitudes of the construction of science in the “periphery” of Europe, in the context of the historiographical category of center-periphery developed by STEP (Science and Technology in the European Periphery), contrasting the reality in Iberia with the model of German science in the period under study.

[Between neurons and synapses: the contributions of Cajal and Athias to Iberian medicine between the nineteenth and twentieth centuries]. / Entre neurônios e sinapses: as contribuições de Cajal e Athias para a medicina ibérica entre os séculos XIX e XX.

The trajectory of histology at the cusp of the twentieth century in Portugal and Spain is investigated to draw a parallel between the contributions of Santiago Ramón y Cajal and Marck Athias, both of whom were instrumental in the development of experimental medicine in the Iberian Peninsula and recognized as pillars of a new European scientific mindset at the dawn of the twentieth century. In this case study we reflect on the vicissitudes of the construction of science in the "periphery" of Europe, in the context of the historiographical category of center-periphery developed by STEP (Science and Technology in the European Periphery), contrasting the reality in Iberia with the model of German science in the period under study.

Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior.

Neonates that suffer oxygen deprivation during birth can have long lasting cognitive deficits, such as memory and learning impairments. Hippocampus, one of the main structures that participate in memory and learning processes, is a plastic and dynamic structure that conserves during life span the property of generating new cells which can become neurons, the so-called neurogenesis. The present study investigated whether a model of rat neonatal anoxia, that causes only respiratory distress, is able to alter the hippocampal volume, the neurogenesis rate and has functional implications in adult life. MRI analysis revealed significant hippocampal volume decrease in adult rats who had experienced neonatal anoxia compared to control animals for rostral, caudal and total hippocampus. In addition, these animals also had 55.7% decrease of double-labelled cells to BrdU and NeuN, reflecting a decrease in neurogenesis rate. Finally, behavioral analysis indicated that neonatal anoxia resulted in disruption of spatial working memory, similar to human condition, accompanied by an anxiogenic effect. The observed behavioral alterations caused by oxygen deprivation at birth might represent an outcome of the decreased hippocampal neurogenesis and volume, evidenced by immunohistochemistry and MRI analysis. Therefore, based on current findings we propose this model as suitable to explore new therapeutic approaches.

Spatial learning and neurogenesis: Effects of cessation of wheel running and survival of novel neurons by engagement in cognitive tasks.

Physical exercise stimulates cell proliferation in the adult dentate gyrus and facilitates acquisition and/or retention of hippocampal-dependent tasks. It is established that regular physical exercise improves cognitive performance. However, it is unclear for how long these benefits last after its interruption. Independent groups of rats received both free access to either unlocked (EXE Treatment) or locked (No-EXE Treatment) running wheels for 7 days, and daily injections of bromodeoxyuridine (BrdU) in the last 3 days. After a time delay period of either 1, 3, or 6 weeks without training, the animals were tested in the Morris water maze (MWM) either in a working memory task dependent on hippocampal function (MWM-HD) or in a visible platform searching task, independent on hippocampal function (MWM-NH). Data confirmed that exposure of rats to 7 days of spontaneous wheel running increases cell proliferation and neurogenesis. In contrast, neurogenesis was not accompanied by significant improvements of performance in the working memory version of the MWM. Longer time delays between the end of exercise and the beginning of cognitive training in the MWM resulted in lower cell survival; that is, the number of novel surviving mature neurons was decreased when this delay was 6 weeks as compared with when it was 1 week. In addition, data showed that while exposure to the MWM-HD working memory task substantially increased survival of novel neurons, exposure to the MWM-NH task did not, thus indicating that survival of novel dentate gyrus neurons depends on the engagement of this brain region in performance of cognitive tasks. © 2015 Wiley Periodicals, Inc.

Homeopatia e integralidade do cuidado dos indivíduos portadores de Hepatite C Crônica / Homeopathy in the integral care of Chronic Hepatitis C carriers

Este artigo tem como principal objetivo discutir as potencialidades da homeopatia para oferecer um cuidado integral aos indivíduos portadores de hepatite C crônica a partir de uma pesquisa realizada no Hospital Universitário Antonio Pedro ­ Niterói/RJ. O quadro metodológico da investigação constou de duas etapas: uma análise quantitativa descritiva de dados obtidos em prontuários de indivíduos portadores de hepatite C crônica durante os primeiros quatorze meses de tratamento homeopático e uma análise qualitativa dos relatos das consultas homeopáticas desses pacientes com enfoque nos sintomas subjetivos. A coleta de dados dessas duas etapas foi realizada durante o ano de 2012. Os resultados da pesquisa quantitativa revelaram que na maior parte dos casos houve uma redução significativa dos principais sintomas apresentados pelos indivíduos: ansiedade, distúrbios do sono, artralgia, mialgia, fraqueza de memória e irritabilidade. Houve também melhoria e estabilidade de três enzimas avaliadas. Na pesquisa qualitativa, sob a ótica de quatro categorias analíticas ­ adesão, resgate da subjetividade, autonomia e mudança de dinâmica vital ­ verificou-se que o tratamento homeopático foi efetivo para a maioria dos participantes dessa pesquisa. Concluiu-se, então, que a especificidade da abordagem homeopática, centrada na pessoa, favoreceu o cuidado e o alívio do sofrimento desses indivíduos.(AU)

This article debates the possibilities of Homeopathy in the integral care of Chronic Hepatitis C carriers. It was outlined on study conducted at the Hospital Universitario Antônio Pedro - Niterói/RJ. The metodology used in this study had two stages, beginning with the quantitative study "Evaluation of the Homeopathic Treatment of Type C Hepatitis Carriers" and a qualitative study which analyzes the reports (subjectives symptoms) contained in the medical records of the individuals who participated in it, during the first 14 months of treatment. Data collection ocurred during 2012. The results of the former revealed that in the majority of the cases there was a significant decrease in the principal symptoms: anxiety, sleep disorders, arthralgia, myalgia, weakness memory, irritability in addition to the improvement and stabilizaton of three enzymes analyzed. Regarding the qualitative study from the viewpoint of four analytical categories - adhesion, subjectivity recovery, autonomy and change in vital dynamics - the study ascertained that the homeopathic treatment was effective for most of the individuals who participated. Therefore, it was concluded that the specificity of the homeopathic approach favored the care and relief of the suffering of Chronic Type C Hepatitis carriers. Keywords: homeopathy, type C hepatitis, integrality in health.(AU)

The neural elements in the lining of the ventricular-subventricular zone: making an old story new by high-resolution scanning electron microscopy.

The classical description of the neural elements that compose the lining of brain ventricles introduces us to the single layer of ependymal cells. However, new findings, especially in the lateral ventricle (LV)-the major niche for the generation of new neurons in the adult brain-have provided information about additional cell elements that influence the organization of this part of the ventricular system and produce important contributions to neurogenesis. To complement the cell neurochemistry findings, we present a three-dimensional in situ description that demonstrates the anatomical details of the different types of ciliated cells and the innervation of these elements. After processing adult rat brains for ultrastructural analysis by high-resolution scanning electron microscopy (HRSEM) and transmission electron microscopy, we observed a heterogeneous pattern of cilia distribution at the different poles of the LV surface. Furthermore, we describe the particular three-dimensional aspects of the ciliated cells of the LV, in addition the fiber bundles and varicose axons surrounding these cells. Therefore, we provide a unique ultrastructural description of the three-dimensional in situ organization of the LV surface, highlighting its innervation, to corroborate the available neurochemical and functional findings regarding the factors that regulate this neurogenic niche.