Guanosine treatment prevents lipopolysaccharide-induced depressive-like behavior in mice.

Guanosine is a purinergic nucleoside that has been shown to have neuroprotective effects, mainly through its ability to modulate the glutamatergic system. An increase in pro-inflammatory cytokine levels triggers the activation of the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), leading to glutamatergic excitotoxicity, which has important roles in the pathophysiology of depression. The aim of this study was to investigate the possible antidepressant-like effects and underlying mechanisms of action of guanosine against lipopolysaccharide (LPS)-induced depression in a mouse model. Mice were orally pre-treated with saline (0.9% NaCl), guanosine (8 or 16 mg/kg), or fluoxetine (30 mg/kg) for 7 days before LPS (0.5 mg/kg, intraperitoneal) injection. One day after LPS injection, mice were subjected to the forced swim test (FST), tail suspension test (TST), and open field test (OFT). After the behavioral tests, mice were euthanized and the levels of tumor necrosis factor-α (TNF-α), IDO-1, glutathione, and malondialdehyde in the hippocampus were measured. Pretreatment with guanosine was able to prevent LPS- induced depressive-like behaviors in the TST and FST. In the OFT, no locomotor changes were observed with any treatment. Both guanosine (8 and 16 mg/kg/day) and fluoxetine treatment prevented the LPS-induced increase in TNF-α and IDO expression and lipid peroxidation as well as decrease of reduced glutathione levels in the hippocampus. Taken together, our findings suggest that guanosine may have neuroprotective effects against LPS-induced depressive-like behavior through preventing oxidative stress and the expression of IDO-1 and TNF-α in the hippocampus.

Involvement of kynurenine pathway and N-methyl-d-aspartate receptors in the antidepressant-like effect of vilazodone in the tail suspension test in mice.

The present study evaluated the antidepressant-like effects of vilazodone using the tail suspension test in mice. We also investigated the contribution of kynurenine pathway and N-methyl-d-aspartate receptors to this effect. For this purpose, we pretreated animals with sub-effective doses of L-kynurenine, 3-hydroxykynurenine, or quinolinic acid. We then assessed the immobility time, an indicative measure of depressive-like behavior, in the tail suspension test. We also evaluated the possible effects of sub-effective doses of vilazodone combined with sub-effective doses of ketamine (N-methyl-d-aspartate receptor antagonist) in a separate group. Vilazodone (3mg/kg, intraperitoneal) significantly reduced immobility time in the tail suspension test. L-kynurenine (1.7 mg/kg, intraperitoneal), 3-hydroxykynurenine (10 mg/kg, intraperitoneal), and quinolinic acid (3 nmol/site, intracerebroventricular) significantly increased the immobility time in the tail suspension test. The antidepressant-like effects of vilazodone (3mg/kg, intraperitoneal) were inhibited by pre-treatment with non-effective doses of L-kynurenine (0.83 mg/kg, intraperitoneal), 3-hydroxykynurenine (3.33 mg/kg, intraperitoneal), or quinolinic acid (1 nmol/site, intracerebroventricular). Pretreatment of mice with sub-effective doses of ketamine (1 mg/kg, intraperitoneal) optimized the action of a sub-effective dose of vilazodone (0.3mg/kg, intraperitoneal) and reduced the immobility time in the tail suspension test. None of the drugs used in this study induced any changes in locomotor activity in the open field test. The results showed that vilazodone induced an antidepressant-like effect in the tail suspension test, which may be mediated through an interaction with the kynurenine pathway and N-methyl-d-aspartate receptors.

Long-term monotherapy treatment with vitamin E reduces oxidative stress, but not seizure frequency in rats submitted to the pilocarpine model of epilepsy.

The imbalance between antioxidant system and reactive oxygen species (ROS) generation is related to epileptogenesis, neuronal death, and seizure frequency. Treatment with vitamin E has been associated with neuroprotection and control of seizures. In most experimental studies, vitamin E treatment has short duration. Therefore, the aim of this study was to verify the role of long-term treatment with vitamin E in rats submitted to the pilocarpine model of epilepsy. Rats were divided into two main groups: control (Ctr) and pilocarpine (Pilo). Each one was subdivided according to treatment: vehicle (Ctr V and Pilo V) or vitamin E at dosages of 6 IU/kg/day (Ctr E6 and Pilo E6) or 60 IU/kg/day (Ctr E60 and Pilo E60). Treatment lasted 120 days from status epilepticus (SE). There were no statistical differences concerning treatment in the Ctr group for all variables, so the data were grouped. Carbonyl content in the hippocampus of Pilo V and Pilo E6 was higher compared with that of the Ctr group (8 ±â€¯1.5, 7.1 ±â€¯1, and 3.1 ±â€¯0.3 nmol carbonyl/mg protein, respectively for Pilo V, Pilo E6, and Ctr; p < 0.05). Carbonyl content was restored to control values in Pilo E60 rats (4.2 ±â€¯1.1 and 3.1 ±â€¯0.3 nmol carbonyl/mg protein, respectively for Pilo E60 and Ctr; p > 0.05). The volume of the hippocampal formation (6.5 ±â€¯0.3, 6.6 ±â€¯0.4, 6.3 ±â€¯0.3, and 7.4 ±â€¯0.2, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) and subfields CA1 (1.6 ±â€¯0.1, 1.4 ±â€¯0.2, 1.5 ±â€¯0.1, and 2 ±â€¯0.05, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) and CA3 (1.7 ±â€¯0.1, 1.5 ±â€¯0.2, 1.4 ±â€¯0.1, and 2 ±â€¯0.1, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) was reduced in the Pilo group regardless of treatment. Parvalbumin immunostaining was increased in the hilus of the Pilo E60 group compared with that in the Ctr group (26 ±â€¯2 and 39.6 ±â€¯8.3 neurons, respectively for Ctr and Pilo E60). No difference was found in seizure frequency and Neo-Timm staining. Therefore, long-term treatment with 60 IU/kg/day of vitamin E prevented oxidative damage in the hippocampus and increased hilar parvalbumin expression in rats with epilepsy without a reduction in seizure frequency.

Altered MT1 and MT2 melatonin receptors expression in the hippocampus of pilocarpine-induced epileptic rats.

Clinical and experimental findings show that melatonin may be used as an adjuvant to the treatment of epilepsy-related complications by alleviates sleep disturbances, circadian alterations and attenuates seizures alone or in combination with AEDs. In addition, it has been observed that there is a circadian component on seizures, which cause changes in circadian system and in melatonin production. Nevertheless, the dynamic changes of the melatoninergic system, especially with regard to its membrane receptors (MT1 and MT2) in the natural course of TLE remain largely unknown. The aim of this study was to evaluate the 24-hour profile of MT1 and MT2 mRNA and protein expression in the hippocampus of rats submitted to the pilocarpine-induced epilepsy model analyzing the influence of the circadian rhythm in the expression pattern during the acute, silent, and chronic phases. Melatonin receptor MT1 and MT2 mRNA expression levels were increased in the hippocampus of rats few hours after SE, with MT1 returning to normal levels and MT2 reducing during the silent phase. During the chronic phase, mRNA expression levels of both receptors return to levels close to control, however, presenting a different daily profile, showing that there is a circadian change during the chronic phase. Also, during the acute and silent phase it was possible to verify MT1 label only in CA2 hippocampal region with an increased expression only in the dark period of the acute phase. The MT2 receptor was present in all hippocampal regions, however, it was reduced in the acute phase and it was found in astrocytes. In chronic animals, there is a reduction in the presence of both receptors especially in regions where there is a typical damage derived from epilepsy. Therefore, we conclude that SE induced by pilocarpine is able to change melatonin receptor MT1 and MT2 protein and mRNA expression levels in the hippocampus of rats few hours after SE as well as in silent and chronic phases.

Pilocarpine-induced epilepsy alters the expression and daily variation of the nuclear receptor RORα in the hippocampus of rats.

It is widely known that there is an increase in the inflammatory responses and oxidative stress in temporal lobe epilepsy (TLE). Further, the seizures follow a circadian rhythmicity. Retinoic acid receptor-related orphan receptor alpha (RORα) is related to anti-inflammatory and antioxidant enzyme expression and is part of the machinery of the biological clock and circadian rhythms. However, the participation of RORα in this neurological disorder has not been studied. The aim of this study was to evaluate the RORα mRNA and protein content profiles in the hippocampus of rats submitted to a pilocarpine-induced epilepsy model at different time points throughout the 24-h light-dark cycle analyzing the influence of the circadian rhythm in the expression pattern during the acute, silent, and chronic phases of the experimental model. Real-time PCR and immunohistochemistry results showed that RORα mRNA and protein expressions were globally reduced in both acute and silent phases of the pilocarpine model. However, 60days after the pilocarpine-induced status epilepticus (chronic phase), the mRNA expression was similar to the control except for the time point 3h after the lights were turned off, and no differences were found in immunohistochemistry. Our results indicate that the status epilepticus induced by pilocarpine is able to change the expression and daily variation of RORα in the rat hippocampal area during the acute and silent phases. These findings enhance our understanding of the circadian pattern present in seizures as well as facilitate strategies for the treatment of seizures.

Estudo do Perfil, Equilíbrio e Prevalência de Quedas em Idosos com Sequela de Acidente Vascular Encefálico / Study of Profile, Balance and Prevalence of Falls in Elderly Patients with Sequel of Cerebrovascular Accident

O acidente vascular encefálico (AVE) é uma síndrome de rápido desenvolvimento com sinais e sintomas clínicos de perda de função cerebral, provocando sequelas motoras e sensitivas-cognitivas. Tais fatores podem provocar redução do equilíbrio, aumentando o risco de quedas. Assim sendo, o propósito deste estudo foi verificar o equilíbrio estático e dinâmico de pacientes com sequela de AVE e a prevalência de quedas. Foi realizado um estudo transversal com indivíduos com sequelas de AVE (hemiparéticos). O equilíbrio estático de dinâmico foi avaliado por meio da Escala de Equilíbrio de Berg, e o equilíbrio durante a marcha em diferentes contextos pelo Índice de Marcha Dinâmica (IMD). A idade média foi de 85 ± 14,1anos, sendo a maioria do sexo masculino (81,8%) e aposentado (82%). Os voluntários apresentaram entre 8 meses e 12 anos de instalação da patologia, todos faziam fisioterapia e a maioria (63,6%) sofreu queda. Foi observado que, em relação aos equilíbrios estático e dinâmico, os pacientes tiveram média de 51,3 ± 6,3 pontos e 45,4% tiveram um escore menor ou igual a 19 pontos no índice de marcha dinâmica, que avalia risco de quedas e 54,5% com escore maior de 19 pontos. Conclui-se que os pacientes com sequela de acidente vascular encefálico apresentam equilíbrio funcional, apesar do risco de quedas.

The cerebrovascular accident is a syndrome of rapid development with clinical signs and symptoms of loss of brain function, causing motor and sensory-cognitive sequels. Such factors may result in decreased balance increasing the risk of falls. Therefore, the purpose of this study was to determine the static and dynamic balance of patients with stroke sequel and the prevalence of falls. A cross-sectional study was conducted with patients with stroke sequel (hemiparesis). The static equilibrium dynamic was evaluated by the Berg Balance Scale and the balance during gait in different contexts by the Dynamic Gait Index (DGI). The middle age was 85 ± 14,1anos, most were men (81.8%) and retired (82.0%). Volunteers presented from 8 months to 12 years of pathology installation, all of them were doing physical therapy and the majority (63.6%) had suffered fall. It was observed that in relation to the static and dynamic balance patients had an average of 51.3 ± 6.3 points and 45.4% had a score less than or equal to 19 points in the dynamic gait index, which assesses risk of falls and 54.5% with the highest score of 19 points. We conclude that patients with stroke sequel have functional balance, although the risk of falls.

Alternativas terapêuticas para tratamento de afecções bucais no idoso / Therapies alternative for the treatment of oral diseases in the elderly

Objetivo: O objetivo deste trabalho foi fazer um levantamento das plantas medicinais utilizadas para tratamento das afecções bucais pelos pacientes idosos atendidos na Faculdade de Odontologia da Universidade de Cuiabá, MT. Metodologia: Foram entrevistados 54 idosos, através de abordagem qualitativa, por meio de entrevista semiestruturada. Resultados: Foram citadas 23 espécies pertencentes a 19 famílias utilizadas na cavidade bucal, encontradas em quintais e no Bioma Cerrado. O maior número de citações correspondeu às espécies: batata doce (Ipomoea batatas (L.) Lam.), romã (Punica granatum L.), hortelã (Mentha piperita L.) e malva(Malva sylvestris L.). As indicações terapêuticas para saúde bucalforam variadas, tais como, inflamações na boca, dor de dente, gengivite,aftas e estomatites, entre outras. A parte da planta mais utilizadafoi a folha e o modo de preparo mais comum, foi o chá por infusão. Conclusão: Os idosos entrevistados utilizavam as plantas medicinais como uma prática terapêutica frequente em saúde bucal, sendo as espécies mais citadas: batata doce (Ipomoea batatas (L.) Lam.), romã (Punica granatum L.), malva (Malva sylvestris L.) e hortelã (Mentha piperita L.). Destas, a hortelã (Mentha piperita L.) recebeu maior indicação terapêutica.

Objective: The aim of this study was to survey the medicinal plants used to treatment of oral diseases by elderly patients assisted in Dental School - University of Cuiabá, MT. Methodology: 54 patients of the clinic were interviewed through qualitative approach using technique of semi-structured interviews. Results: They were cited 23 species belonging to 19 families, used in oral health found in backyards and Cerrado biome. The most cited species were: sweet potato (Ipomoea batatas (L.) Lam.), pomegranete (Punica granatum L.), mint (Mentha piperita L.) and ?malva? (Malva sylvestris L.). The therapeutic indications in oral health were varied, such as, tooth and mouth inflammations, gingivitis,canker sores and stomatitis and others. The leaf was the most used part of the plant and the infusion tea was the most common method of preparation. Conclusion: The elderly interviewed use medicinal plants as a common therapeutic practice for oral health. The most mentioned species; sweet Potato (Ipomoea batatas (L.) Lam.); pomegranate (Punica granatum L.); ?malva? (Malva sylvestris L.) and mint (Mentha piperita L.). From these ones, mint received greater therapeutic indication.

Asma: Idade de Surgimento Pode ser um Fator para o Aumento da Prevalência / Asthma: Age of Onset May be a Factor for the Increased Prevalence

A asma é uma das doenças crônicas mais comuns na população infantil e o aumento da sua prevalência tem se tornado foco de muitas pesquisas epidemiológicas. Nas últimas décadas, observou-se aumento de aproximadamente 50% em sua prevalência, com índices diferentes entre os continentes. Desta forma, o objetivo desse estudo foi fazer uma revisão bibliográfica a respeito da prevalência e idade de surgimento da asma. A presente revisão faz uma abordagem sobre a prevalência, idade de surgimento e fatores de risco em crianças com asma. Foram consultados artigos científicos indexados nas Bases de Dados Scientific Electronic Library Online - SCIELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde - LILACS, e PubMed, utilizando como descritores: asma, surgimento da asma, fatores de risco para asma. Os critérios de elegibilidade foram estudos que apresentassem dados referentes à prevalência da asma, idade de surgimento e fatores de risco para o desenvolvimento, preconizados entre os anos de 1990 até os mais atuais de 2014. As manifestações clínicas surgem, geralmente, na população infantil abaixo de 5 anos de vida, portanto maior atenção individualizada pelos profissionais de saúde deve ser dada às crianças com prováveis diagnósticos de asma, a fim de se propor condutas e estabelecer prognósticos.

Asthma is one of the most common chronic diseases among child population; the increase in its prevalence has become the focus of much epidemiologic research. In recent decades, it was observed an increase of approximately 50% in its prevalence, with different indices among the continents. In this way, the object of our study was making a bibliographic review about the prevalence and the age of onset. This review takes a relevant approach about the prevalence, the age of onset and the risk factors in children with asthma. The research was conducted through a bibliographic review on scientific articles in databases Scientific Electronic Library Online - SciELO, Latin-american and Caribbean Health Sciences - LILACS and PubMed, using as descriptors: asthma, asthma onset, asthma risk factors. The eligibility criteria were studies presenting data relating to asthma prevalence, age of onset, and risk factors, preconized from 1990 to 2014. Clinical manifestations appear usually in the child population under 5 years old, thus, more individualized attention by healthcare professionals must be given to children with probable diagnosis of asthma in order to propose conducts and establish prognostics.

Planejamento Ortodôntico para Pacientes Portadores de Fissuras Labiopalatinas: Revisão de Literatura / Orthodontic Treatment for Patients with Cleft Lip and palate: Literature Review

As fissuras labiopalatinas são defeitos congênitos de origem multifatorial que comprometem a integridade do lábio e/ou palato, determinando alterações funcionais e estéticas. Representam a anomalia mais frequente do complexo craniofacial. Os portadores destas anomalias apresentam maloclusões características, em consequência da atresia dos arcos dentários, principalmente do arco superior, déficit de crescimento do terço médio da face, problemas dentários de anomalias de forma, número e de posição. Os dentes próximos às fissuras podem se apresentar rotacionados, com as coroas inclinadas em direção à fenda e os ápices em direção oposta. Devido à presença de desordens oclusais inerentes à fissura lábio palatina, o tratamento ortodôntico requer protocolo específico para restauração da função e estética. O objetivo deste trabalho foi descrever o planejamento ortodôntico, visando o tratamento multidisciplinar de indivíduos com fissura lábiopalatina. A pesquisa foi realizada a partir da revisão bibliográfica, sendo consultados artigos científicos localizados nas bases de dados de Scientific Electronic Library Online (SCIELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), e PubMed, utilizando como descritores: ?Fenda labial?, ?fissura palatina?, ?ortodontia?, ?má oclusão? no período de 2000 a 2012. Os dados mostram que o tratamento multidisciplinar é fundamental para resolver as necessidades estéticas e funcionais do sistema estomatognático e integrar o paciente na sociedade.

The cleft lip and cleft palate are multifactorial birth defects that compromise the integrity of the lip and / or the palate, determining functional, aesthetic and psychic changes, featuring among the most frequent anomalies of the craniofacial complex. Individuals with cleft lip and palate present malocclusion characteristics due to the atresia of the dental arches, especially in the upper arch, growth deficit in the mid face, dental problems due to anomalies of shape, number and position. The teeth next to the cracks may appear rotated, with crowns tilted toward the summits and rift in the opposite direction. Given the presence of occlusal disorders inherent to the presence of cleft lip and palate, the orthodontic treatment in such patients requires a specific protocol for function and aesthetics restoration. The objective of this paper was to describe the orthodontic planning for the multidisciplinary treatment of individuals with cleft lip and palate. This research was based on the literature review of scientific papers published in journals of Scientific Electronic Library Online (SCIELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), and PubMed, using as keywords: ?cleft lip?, ?cleft palate?, ?orthodontics?, ?malocclusion? in the 2000 - 2012 period. The results showed that the multidisciplinary care is crucial for solving the aesthetic and functional needs of the stomatognathic system and integrate the patient into the society.

Influence of melatonin treatment on the survival and seizures frequency in pilocarpine-induced epilepsy in rats / Influência do tratamento com melatonina na sobrevivência e frequência das crises epiléticas em ratos induzidas por pilocarpina

Objetivo: verificar se o tratamento com melatonina no período crônico pode alterar a frequência de crises e sobrevida de ratos Wistar submetidos ao modelo de epilepsia induzido por pilocarpina. Métodos: os animais foram divididos em dois grupos: Epi+MEL (n=8), animais tratados com melatonina (10 mg/kg) no período crônico; Epi+VEI (n=5), animais tratados com solução veículo no período crônico. Para analisar a duração e a frequência de crises os animais foram vídeo-monitorados antes do tratamento no 5 o e 7o mês de vida e após o início do tratamento no 9°, 11° e 16° mês de vida. Resultados: os animais tratados com melatonina não apresentaram alterações na duração e frequência de crises. Embora tenhamos observado uma taxa de sobrevida de 87,5% nos animais tratados com melatonina e 40% nos animais tratados com veículo, não observamos diferença estatística. Conclusão: o tratamento com melatonina não foi eficaz no controle da frequência e duração das crises, bem como não alterou a sobrevida dos animais. Contudo, acreditamos que a melatonina tenha forte potencial no aumento da expectativa de vida, porém mais estudos são necessários para uma melhor compreensão da sua ação neuroprotetora, bem como seu papel na expectativa de vida...

Objective: to verify if treatment with melatonin in the chronic period can modify the seizures frequency and survival in Wistar rats submitted to pilocarpine-induced model of epilepsy. Methods: animals were divided in two groups: Epi+MEL (n=8) animals treated with melatonin (10 mg / Kg) in the chronic period; EPI+VEH (n=5) animals treated with vehicle solution in the chronic period. To analyze duration and frequency of seizure, all animals were video-monitored during the 5th and 7th month of life and during the treatments in the 9th, 11th and 16th month of life. Results: the animals treated with melatonin in the chronic phase not presented changes in the duration and frequency of seizures. Although, the animals treated with melatonin have shown a survival rate of 87.5% and the animals treated with vehicle 40%, this finding was not statistically significant. Conclusion: Chronic treatment with melatonin was not effective in the control of frequency and duration of seizures, as well did not modify the survival of the animals. Nevertheless, we believe that melatonin has strong potential to increase life expectancy, however, more studies are needed for a better understanding of its neuroprotective action, as well astheir role in life expectancy...

Avaliação da Funcionalidade Motora em Pacientes com Tempo Prolongado de Internação Hospitalar / Evaluation of Motor Functionality in Patients with Prolonged Time of Hospitalization

O prolongado tempo de internação hospitalar, posicionamento inadequado e falta de mobilização predispõe a modificações morfológicas dos músculos e tecidos conjuntivos. Assim, o objetivo desse estudo foi avaliar a funcionalidade motora em pacientes com tempo prolongado de internação hospitalar. Foi realizado um estudo transversal, em pacientes com tempo prolongado de internação hospitalar nas Enfermarias do Hospital Geral Universitário de Cuiabá, maiores de 18 anos, sendo excluídos os pacientes com sequela de acidente vascular encefálico, internados em Unidade de Terapia Intensiva - UTI e com distúrbio cognitivo. Foi registrado o tempo de internação hospitalar e de avaliação da funcionalidade motora através dos testes: Equilíbrio de Berg, Shober, Inclinação lateral e Timed Up and Go (TUG). Participaram do estudo 30 pacientes do sexo feminino e masculino, com idade média de 53,3±17,80 anos; e tempo de internação com média de 14,0±9 dias. O teste de equilíbrio de Berg apresentou valor médio de 45,7±6,8, o teste de Shober e de inclinação lateral direita e esquerda apresentaram respectivamente, média de 15,9±2,2 cm, 50,8±7,9 cm e 52,2±11,1 cm; o equilíbrio de Berg comparado com tempo de internação mostrou uma diferença, porém sem significância estatística (p = 0,79); o teste de TUG comparado ao tempo de internação mostrou que os pacientes com 14,3±10 dias de internação realizaram o teste em menos de 20 segundos e os com média de 13,5±7,78 dias completaram com 30 segundos ou mais. Pacientes com tempo de internação prolongado, maior que sete dias, hospitalizados em enfermarias, não apresentam alteração de equilíbrio, coordenação motora e de independência funcional.

The prolonged hospital stay, improper positioning, and lack of mobilization predisposes the morphological changes of the muscles and connective tissues. The objective of the present study was to assess motor function in patients with prolonged hospitalization. We conducted a cross-sectional study in patients aged over 18 years, with prolonged hospitalization wards in the Hospital Geral Universitário in Cuiabá. We excluded patients with sequelae of stroke, ICU and cognitive impairment. The time of hospitalization and evaluation of motor functionality was registered according to the following tests: Berg Balance, Shober, lateral tilt and TUG. The study included 30 patients, female and male, with mean age of 53.3 ± 17.80 years, and average hospital stay of 14.0 ± 9 days. The Berg Balance test averaged 45.7 ± 6.8, Shober test and lateral right and left showed respectively a mean of 15.9 ± 2.2 cm, 50.8 ± 7.9 cm and 52.2 ± 11.1 cm. No significant difference was observed for the Berg balance as compared with length of stay (p = 0.79). When comparing the TUG test to the stay, patients with 14.3 ± 10 days hospital performed the test in less than 20 seconds, while patients with 13.5 ± 7.78 days completed the test within 30 seconds or more. Patients with prolonged hospitalization time, longer than seven days in hospital wards show no change in balance, motor coordination and functional independence.

Principais Fatores da Baixa Adesão ao Uso do Ácido Fólico / Main Factors Low Adherence to the Use of Folic Acid

Mulheres em idade fértil devem ingerir ácido fólico (folato) para prevenir a má formação do tubo neural no feto. No entanto, fatores como baixa escolaridade, idade, menor nível socioeconômico, número de consultas no pré-natal inferior a sete, tipo de serviço de saúde, despreparo dos profissionais da saúde na orientação e prescrição do folato no período periconcepcional e falta de planejamento da gravidez são determinantes para a não adesão ao uso do ácido fólico. A presente revisão faz uma abordagem relevante sobre os principais fatores que levam ao baixo índice de utilização do folato, eficácia dos programas de fortificação alimentar, conhecimento por parte das gestantes à respeito do seu uso e o papel do pré-natal adequado. A pesquisa foi realizada a partir da revisão bibliográfica, sendo consultados artigos científicos localizados nas bases de dados de Scientific Electronic Library Online (SCIELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Manual de normas técnicas do Ministério da Saúde, Medline e PubMed, utilizando como descritores: ácido fólico, DFTNs (Doenças do Fechamento do Tubo Neural), ácido fólico e defeito no tubo neural, uso de ácido fólico na gestação e Folic Acid and Neural tube defects. Critérios de elegibilidade foram estudos que apresentassem dados referentes a ácido fólico e a prevenção das DFTNs e uso de ácido fólico na gravidez, preconizados entre os anos de 1993 até 2012. Os dados mostram que a suplementação com o folato é de grande relevância na prevenção das DFTNs, porém seu uso ainda é inadequado.

Reproductive-aged women should take folic acid (folate) supplements to prevent the neural tube defect in fetus. However, several factors including the low schooling, age, low socioeconomic status, less than seven prenatal consultations, type of medical health plan, lack of preparation of the medical team regarding the orientation and the prescription of folate during the periconceptional period, and lack of family planning are determinant of the low use of folic acid. This current review makes an important approach to the main factors that lead to the low use of folate, the effectiveness of folic acid food fortification programs, the pregnant's knowledge about the benefits of folate ingestion and the role of the proper prenatal preventive care. This research was based on the literature review of scientific papers published in journals of Scientific Electronic Library Online (SCIELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Manual de normas técnicas do ministério da Saúde (Handbook of technical rules from Brazil´s Heath Department), Medline and PubMed, using as keywords: folic acid, pregnancy and prevention of neural tube defect (NTD). The criteria for the eligibility were studies presenting data regarding folic acid and the prevention of neural tube defect, preconized between 1993 and 2012. These data showed that the folate supplementation has great relevance in the prevention of the neural tube defect (NTD), however their use is still inadequate.

Malnutrition in infancy as a susceptibility factor for temporal lobe epilepsy in adulthood induced by the pilocarpine experimental model.

Malnutrition during the earliest stages of life may result in innumerable brain problems. Moreover, this condition could increase the chances of developing neurological diseases, such as epilepsy. We analyzed the effects of early-life malnutrition on susceptibility to epileptic seizures induced by the pilocarpine model of epilepsy. Wistar rat pups were kept on a starvation regimen from day 1 to day 21 after birth. At day 60, 16 animals (8 = well-nourished; 8 = malnourished) were exposed to the pilocarpine experimental model of epilepsy. Age-matched well-nourished (n = 8) and malnourished (n = 8) rats were used as controls. Animals were video-monitored over 9 weeks. The following behavioral parameters were evaluated: first seizure threshold (acute period of the pilocarpine model); status epilepticus (SE) latency; first spontaneous seizure latency (silent period), and spontaneous seizure frequency during the chronic phase. The cell and mossy fiber sprouting (MFS) density were evaluated in the hippocampal formation. Our results showed that the malnourished animals required a lower pilocarpine dose in order to develop SE (200 mg/kg), lower latency to reach SE, less time for the first spontaneous seizure and higher seizure frequency, when compared to well-nourished pilocarpine rats. Histopathological findings revealed a significant cell density reduction in the CA1 region and intense MFS among the malnourished animals. Our data indicate that early malnutrition greatly influences susceptibility to seizures and behavioral manifestations in adult life. These findings suggest that malnutrition in infancy reduces the threshold for epilepsy and promotes alterations in the brain that persist into adult life.

Melatonin administration after pilocarpine-induced status epilepticus: a new way to prevent or attenuate postlesion epilepsy?

OBJECTIVE: The goal of this study was to verify the effects of treatment with melatonin and N-acetylserotonin on the pilocarpine-induced epilepsy model. METHODS: The animals were divided into four groups: (1) animals treated with saline (Saline); (2) animals that received pilocarpine and exhibited SE (SE); (3) animals that exhibited SE and were treated with N-acetylserotonin (30 minutes and 1, 2, 4, 6, 12, 24, 36, and 48 hours) after SE onset (SE+NAS); (4) animals that exhibited SE and were treated with melatonin at the same time the SE+NAS group (SE+MEL). Behavioral (latency to first seizure, frequency of seizures, and mortality) and histological (Nissl and neo-Timm) parameters were analyzed. RESULTS: The animals treated with melatonin (SE+MEL) had a decreased number of spontaneous seizures during the chronic period (P<0.05), a reduction in mossy fiber sprouting, and less cell damage than the SE group. Animals treated with N-acetylserotonin did not exhibit any kind of significant change. CONCLUSION: Melatonin exerts an important neuroprotective effect by attenuating SE-induced postlesion and promoting a decrease in the number of seizures in epileptic rats. This suggests, for the first time, that melatonin could be used co-therapeutically in treatment of patients exhibiting SE to minimize associated injuries in these situations.

Seizures during pregnancy modify the development of hippocampal interneurons of the offspring.

We investigated the effect of epileptic seizures during pregnancy on hippocampal expression of calcium-binding proteins in the offspring. Female Wistar rats were submitted to the pilocarpine model and mated during the chronic period. Seizure frequency was monitored over the entire pregnancy. Pups were perfused at postnatal days 6 and 13, and the brains processed for Nissl staining and immunohistochemistry for NeuN, calbindin, calretinin, and parvalbumin. Number of stained cells in the hippocampus was estimated through stereological methods. Our results showed a decrease in epileptic seizure frequency during pregnancy. No differences were observed in NeuN-positive, CR-positive cells, and Nissl-stained hippocampal neurons between the groups. However, there was a significant decrease in calbindin-positive cells (P=0.005) and a significant increase in parvalbumin-positive cells (P=0.02) in the experimental group when compared with the control group. These results suggest that seizures during pregnancy affect the development of specific hippocampal interneurons of the offspring.

Melatonin treatment decreases c-fos expression in a headache model induced by capsaicin.

The aim of the present work was to analyze c-fos response within the trigeminal nucleus caudalis (TNC) of pinealectomized rats and animals that received intraperitoneal melatonin, after intracisternal infusion of capsaicin, used to induce intracranial trigeminovascular stimulation. Experimental groups consisted of animals that received vehicle solution (saline-ethanol-Tween 80, 8:1:1, diluted 1:50) only (VEI, n=5); animals that received capsaicin solution (200 nM) only (CAP, n=6); animals submitted to pinealectomy (PX, n=5); sham-operated animals (SH, n=5); animals submitted to pinealectomy followed by capsaicin stimulation (200 nM) after 15 days (PX + CAP, n=7); and animals that received capsaicin solution (200 nM) and intraperitoneal melatonin (10 mg/kg) (CAP + MEL, n=5). Control rats, receiving vehicle in the cisterna magna, showed a small number of c-fos-positive cells in the TNC (layer I/II) as well as the sham-operated and pinealectomized rats, when compared to animals stimulated by capsaicin. On the other hand, pinealectomized rats, which received capsaicin, presented the highest number of c-fos-positive cells. Animals receiving capsaicin and melatonin treatment had similar expression of the vehicle group. Our data provide experimental evidence to support the role of melatonin and pineal gland in the pathophysiology of neurovascular headaches.

Neurogenesis induced by seizures in the dentate gyrus is not related to mossy fiber sprouting but is age dependent in developing rats.

Neurogenesis in the dentate gyrus (DG) has attracted attention since abnormal supragranular mossy fiber sprouting occurs in the same region, in temporal lobe epilepsy. Thus, we submitted developing rats to pilocarpine-induced status epilepticus (SE) to study the relationship between neurogenesis and mossy fiber sprouting. Groups were submitted to SE at: I-P9, II-P7, P8 and P9, III-P17 e IV-P21. Neurogenesis was quantified using BrdU protocol and confirmed through double staining, using neuronal pentraxin. Other animals were monitored by video system until P120 and their brain was studied (Timm and Nissl staining). The neurogenesis at P17 (p=0.007) and P21 (p=0.006) were increased. However, only P21 group showed recurrent seizures and the mossy fiber sprouting in the same region, during adult life, while P17 did not. Thus, our results suggest that neurogenesis is not related to mossy fiber sprouting neither to recurrent spontaneous seizures in pilocarpine model.

Neurogenesis induced by seizures in the dentate gyrus is not related to mossy fiber sprouting but is age dependent in developing rats / A neurogênese induzida por crises no giro denteado não está relacionada ao brotamento de fibras musgosas, mas é dependente da idade, em ratos durante o desenvolvimento

Neurogenesis in the dentate gyrus (DG) has attracted attention since abnormal supragranular mossy fiber sprouting occurs in the same region, in temporal lobe epilepsy. Thus, we submitted developing rats to pilocarpine-induced status epilepticus (SE) to study the relationship between neurogenesis and mossy fiber sprouting. Groups were submitted to SE at: I-P9, II-P7, P8 and P9, III-P17 e IV-P21. Neurogenesis was quantified using BrdU protocol and confirmed through double staining, using neuronal pentraxin. Other animals were monitored by video system until P120 and their brain was studied (Timm and Nissl staining). The neurogenesis at P17 (p=0.007) and P21 (p=0.006) were increased. However, only P21 group showed recurrent seizures and the mossy fiber sprouting in the same region, during adult life, while P17 did not. Thus, our results suggest that neurogenesis is not related to mossy fiber sprouting neither to recurrent spontaneous seizures in pilocarpine model.

A neurogênese no giro dentado tem atraído atenção já que ela ocorre na mesma região do hipocampo que o brotamento das fibras musgosas, na epilepsia do lobo temporal. Assim, submetemos ratos em desenvolvimento ao status epilepticus induzido (SE) por pilocarpine. Grupos foram submetidos em I-P9, II-P7, P8, P9; III-P17 e IV-P21. A neurogênese foi observada usando o protocolo do BrdU e confirmada por dupla marcação com pentraxina neuronal. Outros animais foram monitorados até P120 e seus cérebros analisados (Nissl e Timm). A neurogênese nos grupos P17 (p=0,007) e P21 (p=0,006) aumentaram. Entretanto, o P21 apresentou crises espontâneas e brotamento de fibras musgosas, na mesma região onde ocorreu a neurogênese, enquanto o grupo P17 apresentou somente aumento na neurogênese. Assim, nossos resultados sugerem que o fenômeno da neurogênese não está relacionado com o brotamento de fibras musgosas nem com o aparecimento de crises espontâneas e recorrentes no modelo da pilocarpina.

Serotonin depletion effects on the pilocarpine model of epilepsy.

The monoamine content in cerebral structures has been related to neuronal excitability and several approaches have been used to study this phenomenon during seizure vulnerability. In the present work, we have described the effects of serotonin (5-HT) depletion after the administration of 5,7-dihydroxytryptamine (5,7-DHT) into the median raphe nucleus in rats submitted to the pilocarpine model of epilepsy. Susceptibility to pilocarpine-induced status epilepticus as well as the spontaneous seizure frequency during the chronic period of the model was determined. Since the hippocampus is one of the main structures in the development of this epilepsy model, the 5-HT levels in this region were also determined after drug administration. Sixty-three percent of 5,7-DHT pre-treated rats (15/24) and only 33.4% of those receiving the control solution (9/24) progressed to motor limbic seizures evolving to status epilepticus, following the administration of pilocarpine. The frequency of seizures during the chronic period, in epileptic rats that received 5,7-DHT, showed a significant (58%) increase after the treatment, when compared with control group. Our data showed that serotonin may play an important role on seizure activity which seems to be exerted by its inhibitory action on the expression of overt behavior seizures departing from an established focus in the limbic system.

Cardiovascular protective effect of melatonin in sudden unexpected death in epilepsy: a hypothesis.

Epilepsy is the most common neurological disorder, approximately 1% of the population worldwide have epilepsy. Moreover, sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but potential risk factors include: age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency, AED number and winter temperatures. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. Furthermore, the evidence from the last 10 years suggests that melatonin has an important role in the epileptogenesis process and influences the cardiovascular system as well. The positive effect of melatonin has been demonstrated against different convulsive stimuli in several rodents, including seizures induced by pentylenetetrazole kainate, glutamate, maximal electrical shock and electrically kindled stimulation of amygdala. Clinical studies have also demonstrated a positive role of melatonin on the seizure frequency in children and reduced spiking activity and seizure frequency in patients with intractable epilepsy. In the rat hearts, studies in vivo and in vitro using pharmacological concentrations of melatonin confirmed an anti-arrhythmic effect of this hormone and studies in humans have been shown that chronic heart disease patients have significantly lower melatonin levels in their blood stream than do normal individuals. Thus, caution should be taken in generalization of these findings to epileptic population. Moreover, it is important to note that when dealing with intractable epilepsy that do not respond to any conventional treatment, the additional of melatonin may be evaluated. Taken together, in this paper we suggested a possible relationship between cardiac abnormalities, melatonin and SUDEP.