Maternal hsa-miR-423-5p associated with the cognitive development of babies in pregnant women without mental disorders.

Background: MicroRNAs (miRNAs) are small non-coding RNAs capable of regulating gene expression post-transcriptionally. MiRNAs are recognized as key regulators of diverse biological and developmental processes. During the pregnancy-puerperal cycle, numerous changes occur in the female body for the formation, growth, and development of the baby. After birth, there is a critical period in child development, as rapid gains in the physical, cognitive, and socio-emotional domains constitute the "building blocks" of children's later growth. Objective: The aim of this study was to investigate the association between maternal expression of hsa-miR-423-5p during the first and second trimesters of pregnancy and neurocognitive development at 90 days of life in infants. Methods: This is a longitudinal study included in a population-based cohort study, carried out in a city in southern Brazil. The Bayley III was used to assess the babies' cognitive development. Blood samples from mothers were obtained for RNA extraction from serum and analysis of miRNA expression by qRT-PCR. Results: In total, 87 dyads (mother-baby) were included. The average gestational age was 15.86 weeks (SD ± 5.55). An association of maternal miRNA with infant cognitive development was found; as maternal miR-423-5p increases, infants' cognitive development increases by 2.40 (95% CI 0.37; 4.43, p = 0.021) points at 3 months of age. Conclusion: In this context, it is suggested to use this miRNA as a biomarker of child neurocognitive development detectable in the prenatal period, thus allowing the planning of early interventions.

Acesso transconjutival com cantotomia lateral para abordagem do completo orbito-zigomático-maxilar: relato de caso / Transconjutival access with side cantotomy to approach the orbito-zygomatic-maxillary complex: case report

Objetivo: relatar um caso clínico, embasando os aspectos relativos à técnica cirúrgica transconjutival com cantotomia lateral como tratamento para fratura de COZM. Relato de caso: Paciente, gênero masculino, compareceu ao Serviço de Cirurgia e Traumatologia Bucomaxilofacial do Hospital Geral do Estado (HGE), vítima de acidente motociclístico, apresentando distopia ocular, degrau ósseo em rebordo infraorbitário direito, perda de projeção malar direita, abertura bucal limitada com desvio ipsilateral e distopia oclusal com sinais sugestivos de fratura do complexo-orbito-zigomático-maxilar direito, juntamente com fratura complexa da mandíbula. A abordagem cirúrgica para acessar o COZM contou com a técnica de incisão transconjuntival com cantotomia lateral para uma melhor visualização dos cotos ósseos fraturados. Considerações finais: a escolha por esse tipo de acesso resultou em uma abordagem cirúrgica bem-sucedida, proporcionando segurança na visualização do campo cirúrgico para posterior reabilitação do paciente, estabelecendo uma devolutiva estética e funcional, cicatriz imperceptível e consequentemente um melhor prognóstico para o paciente.(AU)

Objective: to report a clinical case, basing the aspects related to the transconjunctival surgical technique with lateral canthotomy as a treatment for COZM fracture. Case report: Patient, male gender, attended the Oral and Maxillofacial Surgery and Traumatology Service of the General Hospital of the State (HGE), victim of a motorcycle accident, presenting ocular dystopia, bone step in the right infraorbital ridge, loss of right malar projection, mouth opening limited with ipsilateral deviation and occlusal dystopia with signs suggestive of a fracture of the right orbito-zygomatico-maxillary complex along with a complex fracture of the mandible. The surgical approach to access the contoured COZM with the transconjunctival incision technique with lateral canthotomy for better visualization of the fractured bone stumps. Final considerations: the choice for this type of access resulted in a successful behavioral approach, providing security in the experience of the respiratory field for subsequent rehabilitation of the patient, establishing a devolutionary and functional aesthetics, imperceptible healing and, consequently, a better prognosis for the patient.(AU)

Amburana cearensis seed extract stimulates astrocyte glutamate homeostatic mechanisms in hippocampal brain slices and protects oligodendrocytes against ischemia.

BACKGROUND: Stroke is a leading cause of death and disability worldwide. A major factor in brain damage following ischemia is excitotoxicity caused by elevated levels of the neurotransmitter glutamate. In the brain, glutamate homeostasis is a primary function of astrocytes. Amburana cearensis has long been used in folk medicine and seed extract obtained with dichloromethane (EDAC) have previously been shown to exhibit cytoprotective activity in vitro. The aim of the present study was to analyse the activity of EDAC in hippocampal brain slices. METHODS: We prepared a dichloromethane extract (EDAC) from A. cearensis seeds and characterized the chemical constituents by 1H and 13C-NMR. Hippocampal slices from P6-8 or P90 Wistar rats were used for cell viability assay or glutamate uptake test. Hippocampal slices from P10-12 transgenic mice SOX10-EGFP and GFAP-EGFP and immunofluorescence for GS, GLAST and GLT1 were used to study oligodendrocytes and astrocytes. RESULTS: Astrocytes play a critical role in glutamate homeostasis and we provide immunohistochemical evidence that in excitotoxicity EDAC increased expression of glutamate transporters and glutamine synthetase, which is essential for detoxifying glutamate. Next, we directly examined astrocytes using transgenic mice in which glial fibrillary acidic protein (GFAP) drives expression of enhanced green fluorescence protein (EGFP) and show that glutamate excitotoxicity caused a decrease in GFAP-EGFP and that EDAC protected against this loss. This was examined further in the oxygen-glucose deprivation (OGD) model of ischemia, where EDAC caused an increase in astrocytic process branching, resulting in an increase in GFAP-EGFP. Using SOX10-EGFP reporter mice, we show that the acute response of oligodendrocytes to OGD in hippocampal slices is a marked loss of their processes and EDAC protected oligodendrocytes against this damage. CONCLUSION: This study provides evidence that EDAC is cytoprotective against ischemia and glutamate excitotoxicity by modulating astrocyte responses and stimulating their glutamate homeostatic mechanisms.

Can glutathione be a biomarker for suicide risk in women 18 months postpartum?

Background: Suicide risk is prominent among the problems affecting populations, mainly due to the broad family, psychosocial and economic impact. Most individuals at suicidal risk have some mental disorder. There is considerable evidence that psychiatric disorders are accompanied by the activation of neuro-immune and neuro-oxidative pathways. The aim of the study is to evaluate the serum levels of oxidative stress biomarkers in women at risk of suicide after 18 months of postpartum. Methods: This is a case-control study, nested within a cohort study. From this cohort, 45 women [15 without mood disorders and 30 with mood disorders (Major depression and Bipolar disorder)] were selected at 18 months postpartum, the depression and suicide risk were assessed using the Mini-International Neuropsychiatric Interview Plus (MINI-Plus) instrument, module A and C, respectively. Blood was collected and stored for later analysis of the reactive species (DCFH), superoxide dismutase (SOD), and glutathione reduced (GSH). For data analysis, the SPSS program was used. To compare the nominal covariates with the outcome GSH levels, the Student's t-test or analysis of variance (ANOVA) was used. Spearman's correlation was performed for analysis between the quantitative covariates and the outcome. To analyze the interaction between the factors, multiple linear regression was performed. Bonferroni analysis was used as an additional/secondary result to visualize differences in glutathione levels according to risk severity. After the adjusted analysis, p-values < 0.05 were considered statistically significant. Results: The percentage of suicide risk observed in our sample of women at 18 months postpartum was 24.4% (n = 11). After adjusting for the independent variables, only the presence of suicide risk remained associated with the outcome (ß = 0.173; p = 0.007), low levels of GSH at 18 months after postpartum. Likewise, we verified the difference in GSH levels according to the degree of suicide risk, observing a significant association between the differences in glutathione means in the group of women with moderate to high risk compared to the reference group (no suicide risk) (p = 0.009). Conclusion: Our findings suggest that GSH may be a potential biomarker or etiologic factor in women at moderate to high risk of suicide.

Monocrotaline induces acutely cerebrovascular lesions, astrogliosis and neuronal degeneration associated with behavior changes in rats: A model of vascular damage in perspective.

Pyrrolizidine alkaloids (PAs) are secondary plant metabolites playing an important role as phytotoxins in the plant defense mechanisms and can be present as contaminant in the food of humans and animals. The PA monocrotaline (MCT), one of the major plant derived toxin that affect humans and animals, is present in a high concentration in Crotalaria spp. (Leguminosae) seeds and can induce toxicity after consumption, characterized mainly by hepatotoxicity and pneumotoxicity. However, the effects of the ingestion of MCT in the central nervous system (CNS) are still poorly elucidated. Here we investigated the effects of MCT oral acute administration on the behavior and CNS toxicity in rats. Male adult Wistar were treated with MCT (109 mg/Kg, oral gavage) and three days later the Elevated Pluz Maze test demonstrated that MCT induced an anxiolytic-like effect, without changes in novelty habituation and in operational and spatial memory profiles. Histopathology revealed that the brain of MCT-intoxicated animals presented hyperemic vascular structures in the hippocampus, parahippocampal cortex and neocortex, mild perivascular edema in the neocortex, hemorrhagic focal area in the brain stem, hemorrhage and edema in the thalamus. MCT also induced neurotoxicity in the cortex and hippocampus, as revealed by Fluoro Jade-B and Cresyl Violet staining, as well astrocyte reactivity, revealed by immunocytochemistry for glial fibrillary acidic protein. Additionally, it was demonstrated by RT-qPCR that MCT induced up-regulation on mRNA expression of neuroinflammatory mediator, especially IL1ß and CCL2 in the hippocampus and cortex, and down-regulation on mRNA expression of neurotrophins HGDF and BDNF in the cortex. Together, these results demonstrate that the ingestion of MCT induces cerebrovascular lesions and toxicity to neurons that are associated to astroglial cell response and neuroinflammation in the cortex and hippocampus of rats, highlighting CNS damages after acute intoxication, also putting in perspective it uses as a model for cerebrovascular damage.

Central Giant Cell Granuloma in the Mandibular Condyle in a Teenager. A Case Report with Literature Review.

Central giant cell granulomas (CGCG) are not common in the mandibular condyle. In teenagers, the problem is more complex because of difficulties in diagnosis and treatment involving the potential growth of the mandibular process and development of the face. In this short communication a case is presented of an eleven-year-old female under diagnosis of central giant cell granuloma affecting the mandibular condyle treated surgically in two steps using a condylectomy and vertical ramus osteotomy at the first time and later orthognathic surgery, showing the clinical evolution after 13 years of follow-up. In addition, we performed a review of the scientific reports related to CGCG in the mandibular condyle to compare this treatment with others, in terms of follow-up and results. We concluded that the CGCG affecting the mandibular head can be properly treated with low condilectomy, vertical mandibular ramus sliding osteotomy, and discopexy.

Postpartum depression in maternal thyroidal changes.

Evidence in the literature has suggested that there may be an association between thyroid antibodies and depression during pregnancy and in the postpartum period. Thus, this study aims to conduct a systematic review on the prevalence of postpartum depression (PPD) in women with thyroid abnormalities during pregnancy or in the postpartum period. For this review, we used four databases (PubMed, Lilacs, Scielo, and Scopus). Fifteen studies were selected; one study used a case-control design, four used a cross-sectional design and ten utilized prospective cohort designs. All studies were restricted to up to 1 year postpartum, and 46.7% focused on a period between immediate postpartum and 6 months postpartum. Estimates of the prevalence of PPD in pregnant women with thyroid disorders ranged between 8.3% and 36.0%. For follow-up studies, the cumulative incidence of self-reported depression from the primary episode in the first postpartum year was 6.3% in a high-city survey. Although some authors consider the status of positive anti-TPO antibodies to be a possible marker of vulnerability to depression , it is not yet possible to conclude whether thyroid function in the pregnancy-puerperal cycle is involved with the development of PPD.

Manejo cirúrgico de fratura cominutiva de mandíbula por ferimento de arma de fogo: relato de caso / Surgical management of comminuted jaw fracture by firearms injury: case report

Os ferimentos por arma de fogo (FAF) são um grande problema de saúde pública. Na face, a mandíbula é o local de maior incidência, sendo a região de corpo mandibular a mais atingida e as lesões aos tecidos moles frequentemente a ela associadas. Em alguns casos, tais ferimentos apresentam-se de difícil resolução, sobretudo, em casos de fraturas cominutivas e lesões de tecidos moles com alta complexidade. Isso torna o atendimento desses pacientes um desafio para cirurgiões buco-maxilo-faciais. Desta forma, o objetivo deste artigo é relatar um caso de FAF em terço inferior da face, com comprometimento de tecidos moles e mandíbula, pela equipe de Cirurgia e Traumatologia Bucomaxilofacial do Hospital Geral do Estado - Bahia. Paciente de 28 anos de idade, sexo feminino, vítima de FAF em terço inferior da face, por disparo acidental de espingarda. Ao exame clínico, pode-se observar ferimento perfuro-contuso em região de mandíbula e fratura cominutiva de corpo e ângulo mandibular à direita. A paciente foi submetida à cirurgia para remoção de fragmentos ósseos/corpos estranhos, fixação dos cotos com placa de reconstrução 2.4mm e sutura dos planos, em mesmo tempo cirúrgico, reestabelecendo a função da mandíbula. Portanto, devido à fisiopatologia variável dos FAF na mandíbula, não se indica um único padrão de tratamento para as fraturas cominutivas. Além disso, é indispensável o emprego de protocolos de limpeza cirúrgica imediata e antibioticoterapia nos casos com alto grau de cominuição, bem como, sugere-se realizar o tratamento definitivo o mais breve possível(AU)

Firearm injuries (FIs) are a major public health problem. On the face, the mandible is the place with the highest incidence of this trauma, with the mandibular body region being the most affected and the lesions to the soft tissues frequently associated with it. In some cases, such injuries are difficult to resolve, especially in cases of comminuted fractures and soft tissue injuries with high complexity. This makes the care of these patients a challenge for oral and maxillofacial surgeons. Thus, the objective of this article is to report a case of care for a FAF victim in the lower third of the face, with soft tissue and mandible involvement, by the Maxillofacial Surgery and Traumatology team at the Hospital Geral do Estado - Bahia. 28-year-old female patient, victim of FAF in the lower third of the face, due to acidental shotgun firing. On clinical examination, a perforated-blunt wound can be seen in the mandible region and comminuted fracture of the body and angle of the mandible on the right. The patient underwent surgery to remove bone fragments / foreign bodies, fix the stumps with a 2.4 mm reconstruction plate and suture the planes, at the same surgical time, reestablishing the function of the mandible. Therefore, due to the variable pathophysiology of FAF in the mandible, a single treatment pattern is not indicated for comminuted fractures. In addition, it is essential to use immediate surgical cleaning protocols and antibiotic therapy in cases with a high degree of comminution, as well as, it is suggested to carry out the definitive treatment as soon as possible(AU)

JM-20 treatment prevents neuronal damage and memory impairment induced by aluminum chloride in rats.

The number of people with dementia worldwide is estimated at 50 million by 2018 and continues to rise mainly due to increasing aging and population growth. Clinical impact of current interventions remains modest and all efforts aimed at the identification of new therapeutic approaches are therefore critical. Previously, we showed that JM-20, a dihydropyridine-benzodiazepine hybrid molecule, protected memory processes against scopolamine-induced cholinergic dysfunction. In order to gain further insight into the therapeutic potential of JM-20 on cognitive decline and Alzheimer's disease (AD) pathology, here we evaluated its neuroprotective effects after chronic aluminum chloride (AlCl3) administration to rats and assessed possible alterations in several types of episodic memory and associated pathological mechanisms. Oral administration of aluminum to rodents recapitulates several neuropathological alterations and cognitive impairment, being considered a convenient tool for testing the efficacy of new therapies for dementia. We used behavioral tasks to test spatial, emotional- associative and novel object recognition memory, as well as molecular, enzymatic and histological assays to evaluate selected biochemical parameters. Our study revealed that JM-20 prevented memory decline alongside the inhibition of AlCl3 -induced oxidative stress, increased AChE activity, TNF-α and pro-apoptotic proteins (like Bax, caspase-3, and 8) levels. JM-20 also protected against neuronal damage in the hippocampus and prefrontal cortex. Our findings expanded our understanding of the ability of JM-20 to preserve memory in rats under neurotoxic conditions and confirm its potential capacity to counteract cognitive impairment and etiological factors of AD by breaking the progression of key steps associated with neurodegeneration.

Rutin improves glutamate uptake and inhibits glutamate excitotoxicity in rat brain slices.

Rutin is an important flavonoid consumed in the daily diet. It is also known as vitamin P and has been extensively investigated due to its pharmacological properties. On the other hand, neuronal death induced by glutamate excitotoxicity is present in several diseases including neurodegenerative diseases. The neuroprotective properties of rutin have been under investigation, although its mechanism of action is still poorly understood. We hypothesized that the mechanisms of neuroprotection of rutin are associated with the increase in glutamate metabolism in astrocytes. This study aimed to evaluate the protective effects of rutin with a focus on the modulation of glutamate detoxification. We used brain organotypic cultures from post-natal Wistar rats (P7-P9) treated with rutin to evaluate neural cell protection and levels of proteins involved in the glutamate metabolism. Moreover, we used cerebral cortex slices from adult Wistar rats to evaluate glutamate uptake. We showed that rutin inhibited the cell death and loss of glutamine synthetase (GS) induced by glutamate that was associated with an increase in glutamate-aspartate transporter (GLAST) in brain organotypic cultures from post-natal Wistar rats. Additionally, it was observed that rutin increased the glutamate uptake in cerebral cortex slices from adult Wistar rats. We conclude that rutin is a neuroprotective agent that prevents glutamate excitotoxicity and thereof suggest that this effect involves the regulation of astrocytic metabolism.

Neuroimmunomodulatory and Neuroprotective Effects of the Flavonoid Apigenin in in vitro Models of Neuroinflammation Associated With Alzheimer's Disease.

Neurodegenerative disorders (ND) are characterized by the progressive and irreversible loss of neurons. Alzheimer's Disease (AD) is the most incident age-related ND, in which the presence of a chronic inflammatory compound seems to be related to its pathogenesis. Different stimuli in the central nervous system (CNS) can induce activation, proliferation, and changes in phenotype and glial function, which can be modulated by anti-inflammatory agents. Apigenin (4,5,7-trihydroxyflavone) is a flavonoid found in abundance in many fruits and vegetables, that has shown important effects upon controlling the inflammatory response. This study evaluated the neuroprotective and neuroimmunomodulatory potential of apigenin using in vitro models of neuroinflammation associated with AD. Co-cultures of neurons and glial cells were obtained from the cortex of newborn and embryonic Wistar rats. After 26 days in vitro, cultures were exposed to lipopolysaccharide (LPS; 1 µg/ml), or IL-1ß (10 ng/ml) for 24 h, or to Aß oligomers (500 nM) for 4 h, and then treated with apigenin (1 µM) for further 24 h. It was observed that the treatment with apigenin preserved neurons and astrocytes integrity, determined by Rosenfeld's staining and immunocytochemistry for ß-tubulin III and GFAP, respectively. Moreover, it was observed by Fluoro-Jade-B and caspase-3 immunostaining that apigenin was not neurotoxic and has a neuroprotective effect against inflammatory damage. Additionally, apigenin reduced microglial activation, characterized by inhibition of proliferation (BrdU+ cells) and modulation of microglia morphology (Iba-1 + cells), and decreased the expression of the M1 inflammatory marker CD68. Moreover, as determined by RT-qPCR, inflammatory stimuli induced by IL-1ß increased the mRNA expression of IL-6, IL-1ß, and CCL5, and decreased the mRNA expression of IL-10. Contrary, after treatment with apigenin in inflammatory stimuli (IL-1ß or LPS) there was a modulation of the mRNA expression of inflammatory cytokines, and reduced expression of OX42, IL-6 and gp130. Moreover, apigenin alone and after an inflammatory stimulus with IL-1ß also induced the increase in the expression of brain-derived neurotrophic factor (BDNF), an effect that may be associated with anti-inflammatory and neuroprotective effects. Together these data demonstrate that apigenin presents neuroprotective and anti-inflammatory effects in vitro and might represent an important neuroimmunomodulatory agent for the treatment of neurodegenerative conditions.

Reabilitação de maxila atrófica com implantes zigomáticos: relato de caso / Rehabilitation of atrophic maxilla with zygomatic implants: case report

Introdução: maxilas severamente atrofiadas representam um desafio às reabilitações implantossuportadas. A reconstrução maxilar com enxertos ósseos para permitir a reabilitação com implantes osseointegrados é um tratamento com boa previsibilidade e alto índice de sucesso. No entanto, a morbidade causada pela necessidade de regiões doadoras e grande quantidade de osso dificulta a aceitação dos pacientes, podendo, inclusive, ser contraindicada dependendo da condição sistêmica. Objetivos: revisar a literatura, discutir as indicações, as complicações, a previsibilidade das reabilitações com implantes zigomáticos, assim como relatar um caso. Relato de caso: os implantes zigomáticos surgiram como uma alternativa para a reabilitação de pacientes maxilectomizados, decorrente da exérese de tumores, perdas ósseas decorrentes de infecções ou traumas, e casos de atrofia óssea severa, como abordado no caso em questão, em que a paciente apresentava edentulismo total em maxila e não gostaria mais de utilizar a prótese convencional, optando pela prótese sobre implante. Considerações finais: a reabilitação com implantes zigomáticos pode apresentar complicações, como o mau posicionamento dos implantes, comprometendo a reabilitação; todavia, apesar das restrições da técnica, a literatura mostra que os implantes zigomáticos, quando bem indicados, representam uma boa alternativa para a reabilitação de maxilas severamente atrofiadas.(AU)

Introduction: severely atrophied jaws pose a challenge to implant-supported rehabilitations. Maxillary reconstruction with bone graft to allow rehabilitation with implants is a treatment with good predictability and high success rate. However, a morbidity is the disease of the donor regions and the greater amount of bone hinders the acceptance of the patients; including, to be contraindicated depending on the systemic condition. Objectives: this article is a review of the literature, such as the indications, complications, predictability of rehabilitations with zygomatic implants, as well as a case report. Case report: the zygomatic implants appeared as an alternative for the rehabilitation of maxilectomized patients, due to the excision of tumors, bone losses due to infections or trauma and cases of severe bone atrophy, as approached in the case in question, in which the patient had total maxillary edentulism and would no longer like to use the conventional prosthesis, opting for the implant prosthesis. Final considerations: rehabilitation with zygomatic implants may present complications, such as poor placement of implants, compromising rehabilitation; however, despite the limitations of the technique, the literature shows that zygomatic implants, when well indicated, represent a good alternative for the rehabilitation of severely atrophied maxilla.(AU)

JM-20 protects memory acquisition and consolidation on scopolamine model of cognitive impairment.

OBJECTIVE: JM-20, a novel hybrid synthetic molecule, has been reported to have antioxidant, mitoprotective, anti-excitotoxic, anti-apoptotic and anti-inflammatory properties. However, the neuroprotective effect of JM-20 against memory impairment in preclinical AD-like models has not been analyzed. The aim of this study was to evaluate the potential neuroprotection of JM-20 that preserves essential memory process from cholinergic dysfunction and other molecular damages. METHODS: The effects of JM-20 on scopolamine (1 mg/kg)-induced cognitive disorders were studied. Male Wistar rats (220-230 g) were treated with JM-20 and/or scopolamine, and behavioral tasks were performed. The AChE activity, superoxide dismutase activity, catalase activity, MDA and T-SH level on brain tissue were determined by spectrophotometric methods. Mitochondrial functionality parameters were measured after behavioral tests. Histological analyses on hippocampus and prefrontal cortex were processed with hematoxylin and eosin, and neuronal and axonal damage were determined. RESULTS: The behavioral, biochemical and histopathological studies revealed that oral pre-treatment with JM-20 (8 mg/kg) significantly attenuated the scopolamine-induced memory deficits, mitochondrial malfunction, oxidative stress, and prevented AChE hyperactivity probably due to specific inhibition of AChE enzyme. It was also observed marked histological protection on hippocampal and prefrontal-cortex regions. CONCLUSIONS: The multimodal action of this molecule could mediate the memory protection here observed and suggest that it may modulate different pathological aspects of memory deficits associated with AD in humans.

Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats.

Acute liver failure (ALF) implies a severe and rapid liver dysfunction that leads to impaired liver metabolism and hepatic encephalopathy (HE). Recent studies have suggested that several brain alterations such as astrocytic dysfunction and energy metabolism impairment may synergistically interact, playing a role in the development of HE. The purpose of the present study is to investigate early alterations in redox status, energy metabolism and astrocytic reactivity of rats submitted to ALF. Adult male Wistar rats were submitted either to subtotal hepatectomy (92% of liver mass) or sham operation to induce ALF. Twenty-four hours after the surgery, animals with ALF presented higher plasmatic levels of ammonia, lactate, ALT and AST and lower levels of glucose than the animals in the sham group. Animals with ALF presented several astrocytic morphological alterations indicating astrocytic reactivity. The ALF group also presented higher mitochondrial oxygen consumption, higher enzymatic activity and higher ATP levels in the brain (frontoparietal cortex). Moreover, ALF induced an increase in glutamate oxidation concomitant with a decrease in glucose and lactate oxidation. The increase in brain energy metabolism caused by astrocytic reactivity resulted in augmented levels of reactive oxygen species (ROS) and Poly [ADP-ribose] polymerase 1 (PARP1) and a decreased activity of the enzymes superoxide dismutase and glutathione peroxidase (GSH-Px). These findings suggest that in the early stages of ALF the brain presents a hypermetabolic state, oxidative stress and astrocytic reactivity, which could be in part sustained by an increase in mitochondrial oxidation of glutamate.

Alternativas de tratamento para reconstrução de osso frontal: uma série de casos / Treatment alternatives for frontal bone reconstruction: a series of cases

Objetivo: este artigo se propõe a discutir as diferentes modalidades de tratamento de fraturas de osso frontal, demonstradas em uma série de casos clínicos. Relato de casos: três pacientes de gênero variado e com diferentes etiologias de trauma, foram submetidos à cranioplastia, devido a fraturas das corticais externa e interna do osso frontal (além de fixação de outras fraturas de face, em dois dos casos). Nessa série, são apresentados tratamentos com uso de prótese customizada de polimetilmetacrilato, idealizada sobre um protótipo, reconstrução da bossa frontal a partir de telas de titânio e ainda redução óssea com fixação por meio de placas e parafusos. Em todos os casos apresentados, os resultados estéticos e funcionais foram satisfatórios. Considerações finais: baseado no que foi discutido, entendemos que o planejamento deve ser realizado de forma individual e a decisão por qualquer técnica vai depender da gravidade e da extensão da fratura. Para tanto, é necessária uma avaliação criteriosa do caso em questão.(AU)

Objective: This study aims to discuss the different treatment modalities of frontal bone fractures presented in a series of clinical cases. Case report: Three patients of different genders and with different trauma etiologies were subjected to cranioplasty due to fractures of the external and internal cortical of the frontal bone (besides the fixation of other facial fractures, in two of the cases). This series presents treatments using a custom polymethylmethacrylate prosthesis designed on a prototype, the reconstruction of the frontal vault from titanium meshes, and bone reduction with fixation using plates and screws. In all cases presented, the aesthetic and functional results were satisfactory. Final Considerations: The study discussions allow understanding that planning should be performed individually and the decision for any technique will depend on the severity and extent of the fracture. Therefore, a careful assessment of the case in question is required.(AU)

ZIKA Virus and Neuroscience: the Need for a Translational Collaboration.

Zika virus (ZIKV) has become a major challenge for scientists and health agencies. ZIKV's involvement with human fetal microcephaly and Guillain-Barré syndrome and its transmission through Aedes africanus and Aedes aegypti mosquitos highlighted the epidemiological and neurological risks associated to ZIKV infection. In 2013, ZIKV arrives in Brazil but the first outbreak in the country was reported in 2015. Here, we used the Web of Science as a search tool for comparing the evolution of world and Brazilian scientific research on dengue virus (DENV)-also present in mosquito-, ZIKV and microcephaly. The association between ZIKV and microcephaly was only evidenced in 2015. Interestingly, Brazil and the USA are the responsible for most of these reports. Furthermore, the level of double-counted articles indicates a high degree of international collaborative effort in studying ZIKV and microcephaly. The ZIKV research clearly requires multidisciplinary expertise including epidemiologic, clinical, virological, and neurochemical backgrounds. This letter intends to emphasize the need of multidisciplinary studies and put forward some as yet unanswered questions in attempting to contribute to the understanding of this multifaceted health problem. In line with this, we recently constituted a collaborative and multidisciplinary taskforce encompassing eight Brazilian scientific institutions of excellence, The ZIKV translational research taskforce. This taskforce comprises a vast international network of collaborators and welcomes additional collaborators. We intend to advance fast in terms of mechanisms, which can potentially contribute to treat or halt ZIKV spreading around the world.

Cortical Bilateral Adaptations in Rats Submitted to Focal Cerebral Ischemia: Emphasis on Glial Metabolism.

This study was performed to evaluate the bilateral effects of focal permanent ischemia (FPI) on glial metabolism in the cerebral cortex. Two and 9 days after FPI induction, we analyze [18F]FDG metabolism by micro-PET, astrocyte morphology and reactivity by immunohistochemistry, cytokines and trophic factors by ELISA, glutamate transporters by RT-PCR, monocarboxylate transporters (MCTs) by western blot, and substrate uptake and oxidation by ex vivo slices model. The FPI was induced surgically by thermocoagulation of the blood in the pial vessels of the motor and sensorimotor cortices in adult (90 days old) male Wistar rats. Neurochemical analyses were performed separately on both ipsilateral and contralateral cortical hemispheres. In both cortical hemispheres, we observed an increase in tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), and glutamate transporter 1 (GLT-1) mRNA levels; lactate oxidation; and glutamate uptake and a decrease in brain-derived neurotrophic factor (BDNF) after 2 days of FPI. Nine days after FPI, we observed an increase in TNF-α levels and a decrease in BDNF, GLT-1, and glutamate aspartate transporter (GLAST) mRNA levels in both hemispheres. Additionally, most of the unilateral alterations were found only in the ipsilateral hemisphere and persisted until 9 days post-FPI. They include diminished in vivo glucose uptake and GLAST expression, followed by increased glial fibrillary acidic protein (GFAP) gray values, astrocyte reactivity, and glutamate oxidation. Astrocytes presented signs of long-lasting reactivity, showing a radial morphology. In the intact hemisphere, there was a decrease in MCT2 levels, which did not persist. Our study shows the bilateralism of glial modifications following FPI, highlighting the role of energy metabolism adaptations on brain recovery post-ischemia.

Homocysteine Induces Glial Reactivity in Adult Rat Astrocyte Cultures.

Astrocytes are dynamic glial cells associated to neurotransmitter systems, metabolic functions, antioxidant defense, and inflammatory response, maintaining the brain homeostasis. Elevated concentrations of homocysteine (Hcy) are involved in the pathogenesis of age-related neurodegenerative disorders, such as Parkinson and Alzheimer diseases. In line with this, our hypothesis was that Hcy could promote glial reactivity in a model of cortical primary astrocyte cultures from adult Wistar rats. Thus, cortical astrocytes were incubated with different concentrations of Hcy (10, 30, and 100 µM) during 24 h. After the treatment, we analyzed cell viability, morphological parameters, antioxidant defenses, and inflammatory response. Hcy did not induce any alteration in cell viability; however, it was able to induce cytoskeleton rearrangement. The treatment with Hcy also promoted a significant decrease in the activities of Na+, K+ ATPase, superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as in the glutathione (GSH) content. Additionally, Hcy induced an increase in the pro-inflammatory cytokine release. In an attempt to elucidate the putative mechanisms involved in the Hcy-induced glial reactivity, we measured the nuclear factor kappa B (NFκB) transcriptional activity and heme oxygenase 1 (HO-1) expression, which were activated and inhibited by Hcy, respectively. In summary, our findings provide important evidences that Hcy modulates critical astrocyte parameters from adult rats, which might be associated to the aging process.

Peripheral Oxidative Stress Biomarkers in Spinocerebellar Ataxia Type 3/Machado-Joseph Disease.

OBJECTIVES: Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a polyglutamine disorder with no current disease-modifying treatment. Conformational changes in mutant ataxin-3 trigger different pathogenic cascades, including reactive oxygen species (ROS) generation; however, the clinical relevance of oxidative stress elements as peripheral biomarkers of SCA3/MJD remains unknown. We aimed to evaluate ROS production and antioxidant defense capacity in symptomatic and presymptomatic SCA3/MJD individuals and correlate these markers with clinical and molecular data with the goal of assessing their properties as disease biomarkers. METHODS: Molecularly confirmed SCA3/MJD carriers and controls were included in an exploratory case-control study. Serum ROS, measured by 2',7'-dichlorofluorescein diacetate (DCFH-DA) as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) antioxidant enzyme activities, levels were assessed. RESULTS: Fifty-eight early/moderate stage symptomatic SCA3/MJD, 12 presymptomatic SCA3/MJD, and 47 control individuals were assessed. The DCFH-DA levels in the symptomatic group were 152.82 nmol/mg of protein [95% confidence interval (CI), 82.57-223.08, p < 0.001] higher than in the control and 243.80 nmol/mg of protein (95% CI, 130.64-356.96, p < 0.001) higher than in the presymptomatic group. The SOD activity in the symptomatic group was 3 U/mg of protein (95% CI, 0.015-6.00, p = 0.048) lower than in the presymptomatic group. The GSH-Px activity in the symptomatic group was 13.96 U/mg of protein (95% CI, 5.90-22.03, p < 0.001) lower than in the control group and 20.52 U/mg of protein (95% CI, 6.79-34.24, p < 0.001) lower than in the presymptomatic group and was inversely correlated with the neurological examination score for spinocerebellar ataxias (R = -0.309, p = 0.049). CONCLUSION: Early/moderate stage SCA3/MJD patients presented a decreased antioxidant capacity and increased ROS generation. GSH-Px activity was the most promising oxidative stress disease biomarker in SCA3/MJD. Further longitudinal studies are necessary to identify both the roles of redox parameters in SCA3/MJD pathophysiology and as surrogate outcomes for clinical trials.