Progress in application of adult endogenous neurogenesis in brain injury repair / 生理学报

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.

Research on electroencephalogram power spectral density of stroke patients under transcranial direct current stimulation / 生物医学工程学杂志

Transcranial direct current stimulation (tDCS) has become a new method of post-stroke rehabilitation treatment and is gradually accepted by people. However, the neurophysiological mechanism of tDCS in the treatment of stroke still needs further study. In this study, we recruited 30 stroke patients with damage to the left side of the brain and randomly divided them into a real tDCS group (15 cases) and a sham tDCS group (15 cases). The resting EEG signals of the two groups of subjects before and after stimulation were collected, then the difference of power spectral density was analyzed and compared in the band of delta, theta, alpha and beta, and the delta/alpha power ratio (DAR) was calculated. The results showed that after real tDCS, delta band energy decreased significantly in the left temporal lobes, and the difference was statistically significant ( P < 0.05); alpha band energy enhanced significantly in the occipital lobes, and the difference was statistically significant ( P < 0.05); the difference of theta and beta band energy was not statistically significant in the whole brain region ( P > 0.05). Furthermore, the difference of delta, theta, alpha and beta band energy was not statistically significant after sham tDCS ( P > 0.05). On the other hand, the DAR value of stroke patients decreased significantly after real tDCS, and the difference was statistically significant ( P < 0.05), and there was no significant difference in sham tDCS ( P > 0.05). This study reveals to a certain extent the neurophysiological mechanism of tDCS in the treatment of stroke.

Proteome profiling of different rat brain regions reveals the modulatory effect of prolonged maternal separation on proteins involved in cell death-related processes

BACKGROUND: Early-life stress in the form of maternal separation can be associated with alterations in offspring neurodevelopment and brain functioning. Here, we aimed to investigate the potential impact of prolonged maternal separation on proteomic profiling of prefrontal cortex, hippocampus and cerebellum of juvenile and young adult rats. A special attention was devoted to proteins involved in the process of cell death and redox state maintenance. METHODS: Long-Evans pups were separated from their mothers for 3 h daily over the first 3 weeks of life (during days 2-21 of age). Brain tissue samples collected from juvenile (22-day-old) and young adult (90-day-old) rats were used for label-free quantitative (LFQ) proteomic analysis. In parallel, selected oxidative stress markers and apoptosis-related proteins were assessed biochemically and by Western blot, respectively. RESULTS: In total, 5526 proteins were detected in our proteomic analysis of rat brain tissue. Approximately one tenth of them (586 proteins) represented those involved in cell death processes or regulation of oxidative stress balance. Prolonged maternal separation caused changes in less than half of these proteins (271). The observed alterations in protein expression levels were age-, sex- and brain region-dependent. Interestingly, the proteins detected by mass spectrometry that are known to be involved in the maintenance of redox state were not markedly altered. Accordingly, we did not observe any significant differences between selected oxidative stress markers, such as the levels of hydrogen peroxide, reduced glutathione, protein carbonylation and lipid peroxidation in brain samples from rats that underwent maternal separation and from the corresponding controls. On the other hand, a number of changes were found in cell death-associated proteins, mainly in those involved in the apoptotic and autophagic pathways. However, there were no detectable alterations in the levels of cleaved products of caspases or Bcl-2 family members. Taken together, these data indicate that the apoptotic and autophagic cell death pathways were not activated by maternal separation either in adolescent or young adult rats. CONCLUSIONS: Prolonged maternal separation can distinctly modulate expression profiles of proteins associated with cell death pathways in prefrontal cortex, hippocampus and cerebellum of juvenile rats and the consequences of early-life stress may last into adulthood and likely participate in variations in stress reactivity.

Clinical and subclinical maternal hypothyroidism and their effects on neurodevelopment, behavior and cognition

ABSTRACT Clinical and subclinical hypothyroidism are the most common hormonal dysfunctions during pregnancy. Insufficient maternal thyroid hormones (THs) in the early stages of pregnancy can lead to severe impairments in the development of the central nervous system because THs are critical to central nervous system development. In the fetus and after birth, THs participate in neurogenic processes, cell differentiation, neuronal activation, axonal growth, dendritic arborization, synaptogenesis and myelination. Although treatment is simple and effective, approximately 30% of pregnant women in Brazil with access to prenatal care have their first consultation after the first trimester of pregnancy, and any delay in diagnosis and resulting treatment delay may lead to cognitive impairment in children. This review summarizes the effects of clinical and subclinical hypothyroidism on fetal neurodevelopment, behavior and cognition in humans and rodents. Arch Endocrinol Metab. 2020;64(1):89-95

Preterm infants with peri/intraventricular hemorrhage have poorer habituation responses to external stimuli / Neonatos prematuros com hemorragia peri-intraventricular apresentam respostas de habituação piores a estímulos externos

ABSTRACT Objective: To evaluate the association between intra-ventricular hemorrhage and habituation responses to external stimuli in preterm infants at 36-38 weeks post-conceptual age. Methods: Cross-sectional study of infants with gestational age <32 weeks. Intra-ventricular hemorrhage was identified by cranial ultrasonography and classified according to Papile et al. (1978). The luminous (flashlight), sound (rattle, bell), and tactile stimuli were presented, and the responses were scored according to Lester and Tronik (2004). Habituation response scores were compared between groups by Student's t-test. The association between IVH and habituation scores was evaluated by linear regression adjusted for GA, clinical severity score, post-conceptual age at habituation assessment, sepsis, and bronchopulmonary dysplasia. Results: Sixty-five infants were studied, 20 with intra-ventricular hemorrhage (16 grades I/II; four grades III/IV) and 45 without intra-ventricular hemorrhage. Infants with intra-ventricular hemorrhage had lower gestational age (28.2 ± 2.2 vs. 29.7 ± 1.7 weeks) and birth weight (990 ± 305 vs. 1275 ± 360 g). Infants with intra-ventricular hemorrhage at 36-38 weeks post-conceptual age had lower habituation scores to light (4.21 ± 2.23 vs. 6.09 ± 2.44), rattle (3.84 ± 2.12 vs. 6.18 ± 2.27), and bell (3.58 ± 1.74 vs. 5.20 ± 2.47) after controlling for confounders. No differences were found for tactile stimulus. Conclusion: Infants with gestational age <32 weeks and intra-ventricular hemorrhage had poorer habituation responses to external stimuli than those without intra-ventricular hemorrhage at 36-38 weeks post-conceptual age.

RESUMO Objetivo: Avaliar a associação entre hemorragia intraventricular e as respostas de habituação a estímulos externos em neonatos prematuros com idade pós-conceptual de 36-38 semanas. Métodos: Estudo transversal com neonatos com idade gestacional < 32 semanas. A hemorragia intraventricular foi identificada por ultrassonografia craniana e classificada de acordo com Papile et al. (1978). Os estímulos luminosos (lanterna), sonoros (chocalho, sino) e táteis foram apresentados e as respostas foram pontuadas de acordo com Lester & Tronik (2004). Os escores das respostas de habituação foram comparadas entre os grupos pelo teste t de Student. A associação entre a hemorragia intraventricular e os escores de habituação foi avaliada por regressão linear ajustada para a idade gestacional, escore de gravidade clínica, idade pós-conceptual na avaliação da habituação, sepse e displasia broncopulmonar. Resultados: 65 neonatos foram estudados, 20 com hemorragia intraventricular (16 graus I/II;4 graus III/IV) e 45 sem hemorragia intraventricular. Os neonatos com hemorragia intraventricular apresentaram menor idade gestacional (28,2 ± 2,2 vs. 29,7 ± 1,7 semanas) e peso ao nascer (990 ± 305 vs. 1275 ± 360 g). Os neonatos com hemorragia intraventricular na idade pós-conceptual de 36-38 semanas apresentaram escores de habituação menores a luz (4,21 ± 2,23 vs. 6,09 ± 2,44), chocalho (3,84 ± 2,12 vs. 6,18 ± 2,27) e campainha (3,58 ± 1,74 vs. 5,20 ± 2,47) após controle para variáveis de confusão. Nenhuma diferença foi encontrada para os estímulos táteis. Conclusão: Neonatos com idade gestacional < 32 semanas e hemorragia intraventricular apresentaram respostas de habituação piores a estímulos externos que os sem hemorragia intraventricular, na idade pós-conceptual de 36-38 semanas.

Enfermedades desmielinizantes en niños: Encefalomielitis diseminada aguda y esclerosis múltiple / Demyelinizing diseases in children. Acute disseminated encephalomyelitis and multiple sclerosis

Se revisan dos de las principales enfermedades desmielinizantes en niños, la encefalomielitis aguda diseminada (EAD) y la esclerosis múltiple (EM). Por sus características fisiopatológicas, etiologías probables, manifestaciones clínicas, diagnóstico, tratamiento, pronóstico, evolución, así como alteraciones atípicas que complican su diagnóstico; cuanto más pequeño es el paciente se necesita estudiar más, antes de llegar al diagnóstico. El Grupo Internacional de Estudio de Esclerosis Múltiple Pediátrica publicó las definiciones operativas para enfermedades desmielinizantes adquiridas del sistema nervioso central: la EAD es monofásica, polisintomática y con encefalopatía. Su duración es de hasta 3 meses, con síntomas fluctuantes y hallazgos en resonancia magnética. La EM se define como síndrome aislado monofocal o polifocal, sin encefalopatía. Actualmente se consideran dos enfermedades diferentes y distinguibles desde el inicio de los síntomas.

The two main demyelinating diseases in children are reviewed. Acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS). For its physiopathological characteristics, probable etiologies, clinical manifestations, diagnosis, treatment, prognosis, evolution, as well as atypical alterations that complicate its diagnosis, the smaller the child is, more study is needed before reaching the diagnosis. The International Study Group of Multiple Pediatric Sclerosis, published the operating definitions for demyelinating diseases acquired from the central nervous system in children: the ADEM is monophasic, polysymptomatic and with encephalopathy. Its duration is up to 3 months, with fluctuating symptoms and magnetic resonance findings. MS is an isolated monofocal or polyfocal syndrome, without encephalopathy. Currently, two different and distinguishable diseases are considered from the onset of symptoms.

Structural and functional neuroimaging studies in generalized anxiety disorder: a systematic review

Objectives: Brain imaging studies carried out in patients suffering from generalized anxiety disorder (GAD) have contributed to better characterize the pathophysiological mechanisms underlying this disorder. The present study reviews the available functional and structural brain imaging evidence on GAD, and suggests further strategies for investigations in this field. Methods: A systematic literature review was performed in PubMed, PsycINFO, and Google Scholar, aiming to identify original research evaluating GAD patients with the use of structural and functional magnetic resonance imaging as well as diffusion tensor imaging. Results: The available studies have shown impairments in ventrolateral and dorsolateral prefrontal cortex, anterior cingulate, posterior parietal regions, and amygdala in both pediatric and adult GAD patients, mostly in the right hemisphere. However, the literature is often tentative, given that most studies have employed small samples and included patients with comorbidities or in current use of various medications. Finally, different methodological aspects, such as the type of imaging equipment used, also complicate the generalizability of the findings. Conclusions: Longitudinal neuroimaging studies with larger samples of both juvenile and adult GAD patients, as well as at risk individuals and unaffected relatives, should be carried out in order to shed light on the specific biological signature of GAD.

Convulsiones neonatales: Diagnóstico clínico y electroencefalográfico / Neonatal seizures. Clinical and electroencephalographic diagnosis

Las convulsiones neonatales son una expresión común de lesiones cerebrales agudas durante el periodo perinatal y podrían incrementar el daño neuronal. La mayoría son electroencefalográficas y las clínicas pueden ser sutiles y difíciles de identificar por el personal médico. Las convulsiones neonatales son usualmente cortas pero frecuentes al inicio y tienden a desaparecer en un periodo corto. El video-EEG continuo es el test ideal para detectar estas convulsiones, pero el EEG de amplitud es útil cuando el EEG convencional no está disponible. El monitoreo con EEG no solo es necesario para evaluar la frecuencia y duración de estas convulsiones, también puede proporcionar información pronóstica importante.

Neonatal seizures are common expression of acute brain injury in the perinatal period and could potentiate the degree of neuronal injury. The majority of events are electroencephalographic and the clinical seizures can be subtle and difficult to identify by medical personnel. Neonatal seizures are usually short and frequent at onset and have a tendency to subside after a short period. Continuous video-EEG monitoring is the gold standard to detect seizures, but amplitude integrated EEG is a useful tool when conventional EEG is not available. EEG monitoring is important not only to monitor frequency and duration of seizures but to provide important prognostic information.

Epilepsia asociada al accidente cerebrovascular / Post-stroke epilepsy

El accidente cerebrovascular (ACV) es la causa más común de convulsiones y epilepsia observada en estudios poblacionales de adultos. Las convulsiones ocurren dentro de las 24 horas posteriores al ACV en un alto porcentaje de pacientes. La patogénesis de estas convulsiones de inicio temprano puede estar relacionada con cambios iónicos locales y liberación de altos niveles de neurotransmisores excito-tóxicos en el área lesionada. Una lesión permanente con cambios en la excitabilidad neuronal parece ser responsable de convulsiones de inicio tardío después del ACV. Los factores de riesgo más comúnmente identificados con el comienzo agudo o tardío de las convulsiones post ACV son la gravedad y la localización cortical. La mayoría de las convulsiones post ACV son focales al inicio pero pueden generalizarse secundariamente, el estatus epiléptico es poco frecuente. La eficacia de las drogas antiepilépticas para estas convulsiones no ha sido rigurosamente evaluada en estudios controlados, aunque la mayoría de las convulsiones pueden ser controladas con un solo agente. Dada la frecuencia relativamente baja de convulsiones recurrentes después del ACV y la ausencia de predictores absolutos de epilepsia post ACV, la decisión de cuándo tratar a los pacientes con una convulsión después de un ACV es difícil.

Stroke is the most common cause of seizures and epilepsy in population stuies of adults. Seizures occur within 24 hours of the stroke in a high percent of patients. The pathogenesis of these early-onset seizures may be related to local ion shifts and release of high levels of excitotoxic neurotransmitters in the area of ischemic injury. The risk of late-onset seizures may increase over time, an underlying permanent lesion that leads to persistent chnges in neuronal excitability appears to be responsible for late-onset seizures after stroke. The most consistently identified risk factors for acute and late post-stroke seizures are stroke severity and cortical location. Most seizures following stroke are focal at onset, but secondary generalization is common, particularly in patients with late-onset seizures. Status epilepticus is relatively uncommon. The efficacy of antiepileptic drugs for these post-stroke seizures has not been rigorously assessed in controlled trials, although most seizures can be controlled with a single agent. Given the relatively low frequency of recurrent seizures after stroke, and an absence of absolute predictors of poststroke epilepsy, the decision of when to treat patients for a post-stroke seizure is difficult.

Subprodutos do metabolismo da hemoglobina se associam com resposta inflamatória em pacientes com acidente vascular cerebral hemorrágico / Hemoglobin metabolism by-products are associated with an inflammatory response in patients with hemorrhagic stroke

RESUMO Objetivo: Avaliar o relacionamento entre os níveis cerebrais de ferro e heme e a resposta inflamatória sistêmica e no sistema nervoso central, assim como o papel dos sistemas de defesa contra a toxicidade do ferro e do heme, no sistema nervoso central. Métodos: Avaliamos uma coorte prospectiva de pacientes com quadro de hemorragia intracraniana e subaracnóidea. Realizamos ensaios em amostras de plasma e líquido cefalorraquidiano quanto à presença de ferro, heme, hemopexina, haptoglobina, enolase, S100-β e citocinas nos primeiros 3 dias após um acidente vascular cerebral hemorrágico. Analisamos também as alterações dinâmicas em todos os componentes de ambos os líquidos e seu relacionamento com as taxas de mortalidade precoce. Resultados: As concentrações de hemopexina e haptoglobina foram quase desprezíveis no cérebro após hemorragia intracraniana e subaracnóidea. As concentrações de ferro e heme no líquido cefalorraquidiano se correlacionaram com resposta pró-inflamatória no sistema nervoso central, e os perfis inflamatórios no líquido cefalorraquidiano no terceiro dia após acidente vascular cerebral hemorrágico se correlacionaram com as taxas de mortalidade precoce. Identificamos que os níveis de interleucina 4 no líquido cefalorraquidiano durante as primeiras 24 horas após acidente vascular cerebral hemorrágico foram mais altos nos sobreviventes do que nos que não sobreviveram. Conclusão: Os níveis de ferro e heme se associaram com resposta pró-inflamatória no sistema nervoso central após acidente vascular cerebral hemorrágico, e o cérebro humano não tem proteção contra hemoglobina e heme. Os perfis inflamatórios dos pacientes se associaram com prognósticos piores, e as respostas inflamatórias locais pareceram ter um papel protetor.

ABSTRACT Objective: To evaluate the relationships of brain iron and heme with the inflammatory response of the systemic and central nervous systems and to investigate the role of defensive systems against the toxicity of iron and heme in the central nervous system. Methods: We assessed a prospective cohort of patients presenting with intracerebral and subarachnoid hemorrhage. We assayed plasma and cerebrospinal fluid samples for the presence of iron, heme, hemopexin, haptoglobin, enolase, S100-β and cytokines for the first three days following hemorrhagic stroke. We also analyzed the dynamic changes in these components within both fluids and their relationship with early mortality rates. Results: Hemopexin and haptoglobin concentrations were nearly negligible in the brain after intracerebral and subarachnoid hemorrhage. Cerebrospinal fluid iron and heme concentrations correlated with a pro-inflammatory response in the central nervous system, and plasmatic and cerebrospinal fluid inflammatory profiles on the third day after hemorrhagic stroke were related to early mortality rates. Interleukin 4 levels within the cerebrospinal fluid during the first 24 hours after hemorrhagic stroke were found to be higher in survivors than in non-survivors. Conclusion: Iron and heme are associated with a pro-inflammatory response in the central nervous system following hemorrhagic stroke, and protections against hemoglobin and heme are lacking within the human brain. Patient inflammatory profiles were associated with a poorer prognosis, and local anti-inflammatory responses appeared to have a protective role.

Role of aquaporin-4 in the change of interstitial fluid drainage in Alzheimer's disease / 北京大学学报(医学版)

OBJECTIVE@#To observe the characteristics of the interstitial fluid (ISF) drainage in the Alzheimer's disease (AD) rats through magnetic resonance imaging (MRI) tracer gadolinium-diethylene triamine pentacetic acid (Gd-DTPA)spread in the brain extracellular space (ECS) and to discuss the role of aquaporin-4 (Aqp4) in the AD.@*METHODS@#Wild type SD rats (300-350 g) and Aqp4 gene knock out (Aqp4-/-) SD rats (300-350g) were divided into Sham group, AD group, Aqp4-/--Sham group and Aqp4-/--AD group. Sham group and Aqp4-/--Sham group were injected with saline by intraperitoneal each day for 6 weeks, and the AD group and Aqp4-/--AD group were injected with D-galactose by intraperitoneal each day for 6 weeks. MRI tracer Gd-DTPA (10 mmol/L, 2 μL) was injected into the hippocampus of the rats. MRI scan was performed at the end of 0.5 h, 1.5 h, 1 h, 2 h, and 3 h to observe the dynamic distribution of the Gd-DTPA in the hippocampus and the diffusion rate D*, clearance rate k' and half-life t1/2 measured.@*RESULTS@#The diffusion rate D* in Sham group was (2.66±0.36)×10-6 mm2/s, the diffusion rate D* in AD group was (2.72±0.62)×10-6 mm2/s, the diffusion rate D* in Aqp4-/--Sham group was (2.75±0.47)×10-6 mm2/s, the diffusion rate D* in Aqp4-/--AD group was (2.802±0.55)×10-6 mm2/s, and there was no statistically significant difference in the four groups (One-Way ANOVA, P>0.05).The clearance rate k' in Sham group was (4.57±0.14)×10-4/s, the clearance rate k' in AD group was (3.68±0.22)×10-4/s, the clearance rate k' in Aqp4-/--Sham group was (3.17±0.16)×10-4/s, the clearance rate k' in Aqp4-/--AD group was (2.59±0.19)×10-4/s, and there was significant difference in the four groups (One-Way ANOVA, P<0.05). The half-life t1/2 in Sham group was (0.67±0.12) h, the half-life t1/2 in AD group was (0.88±0.08) h, the half-life t1/2 in Aqp4-/--Sham group was (1.12±0.15) h, the half-life t1/2 in Aqp4-/--AD group was (1.58±0.11) h, and there was significance difference in the four groups(one-way ANOVA,P<0.05).@*CONCLUSION@#The ISF drainage is slow after AD and the loss of Aqp4 in the AD makes the ISF drainage obviously slow down, Aqp4 plays an important role in AD to remove the metabolism of waste out of the brain.

Computerized cognitive training in children and adolescents with attention deficit/hyperactivity disorder as add-on treatment to stimulants: feasibility study and protocol description / Treinamento cognitivo para crianças e adolescentes com transtorno de déficit de atenção/hiperatividade como tratamento complementar aos psicoestimulantes: estudo de viabilidade e descrição de protocolo

Abstract Background Cognitive training has received increasing attention as a non-pharmacological approach for the treatment of attention deficit/hyperactivity disorder (ADHD) in children and adolescents. Few studies have assessed cognitive training as add-on treatment to medication in randomized placebo controlled trials. The purpose of this preliminary study was to explore the feasibility of implementing a computerized cognitive training program for ADHD in our environment, describe its main characteristics and potential efficacy in a small pilot study. Methods Six ADHD patients aged 10-12-years old receiving stimulants and presenting residual symptoms were enrolled in a randomized clinical trial to either a standard cognitive training program or a controlled placebo condition for 12 weeks. The primary outcome was core ADHD symptoms measured using the Swanson, Nolan and Pelham Questionnaire (SNAP-IV scale). Results We faced higher resistance than expected to patient enrollment due to logistic issues to attend face-to-face sessions in the hospital and to fill the requirement of medication status and absence of some comorbidities. Both groups showed decrease in parent reported ADHD symptoms without statistical difference between them. In addition, improvements on neuropsychological tests were observed in both groups - mainly on trained tasks. Conclusions This protocol revealed the need for new strategies to better assess the effectiveness of cognitive training such as the need to implement the intervention in a school environment to have an assessment with more external validity. Given the small sample size of this pilot study, definitive conclusions on the effects of cognitive training as add-on treatment to stimulants would be premature.

Resumo Introdução O treinamento cognitivo tem recebido atenção especial como abordagem não medicamentosa para o tratamento do transtorno de déficit de atenção/hiperatividade (TDAH) em crianças e adolescentes. Poucos estudos avaliaram o treinamento cognitivo como abordagem complementar à medicação em ensaios clínicos randomizados controlados por placebo. O objetivo deste estudo foi explorar a viabilidade para a implementação de um programa de treinamento cognitivo computadorizado, descrever suas características principais e potencial eficácia em um pequeno estudo piloto. Métodos Seis pacientes com TDAH entre 10-12 anos de idade, em uso de psicoestimulantes e apresentando sintomas residuais, foram recrutados e randomizados para um dos dois grupos (treinamento cognitivo ou placebo) por 12 semanas. O desfecho principal foram os sintomas nucleares do TDAH avaliados através do Questionário de Swanson, Nolan e Pelham (SNAP-IV). Resultados Encontramos maior resistência do que a esperada no recrutamento dos pacientes em função de problemas logísticos para atender às sessões presenciais no hospital assim como para preencherem os critérios de status medicamentoso e ausência de algumas comorbidades. Ambos os grupos apresentaram diminuição nos escores dos sintomas de TDAH reportados pelos pais, mas sem diferença estatística entre eles. Além disso, foi observada melhora nos testes neuropsicológicos em ambos os grupos - principalmente nas tarefas treinadas pelo programa. Conclusão Este protocolo revelou a necessidade de novas estratégias para melhor avaliar a eficácia do treinamento cognitivo tal como a necessidade de implementar a intervenção no ambiente escolar a fim de obter uma avaliação com maior validade externa. Devido ao pequeno tamanho amostral deste estudo, conclusões definitivas sobre os efeitos do treinamento cognitivo como abordagem complementar aos psicoestimulantes seriam prematuras.

Electroencephalographic findings in patients with major depressive disorder during cognitive or emotional tasks: a systematic review

Objective: Major depressive disorder (MDD) is a prevalent psychiatric condition characterized by multiple symptoms that cause great distress. Uncovering the brain areas involved in MDD is essential for improving therapeutic strategies and predicting response to interventions. This systematic review discusses recent findings regarding cortical alterations in depressed patients during emotional or cognitive tasks, as measured by electroencephalography (EEG). Methods: A search of the MEDLINE/PubMed and Cochrane databases was carried out using the keywords EEG and depression, confined to article title. Results: The studies identified reveal the frontal cortex as an important brain structure involved in the complex neural processes associated with MDD. Findings point to disorganization of right-hemisphere activity and deficient cognitive processing in MDD. Depressed individuals tend to ruminate on negative information and respond with a pattern of relatively higher right frontal activity to emotional stimuli associated with withdrawal and isolation. Conclusion: Patients with MDD may have altered dynamic patterns of activity in several neuroanatomical structures, especially in prefrontal and limbic areas involved in affective regulation. Identification of these alterations might help predict the response of patients to different interventions more effectively and thus maximize the effects both of pharmacotherapeutic and of psychotherapeutic strategies.

Progress on Correlation between the Expression of CDK5 and Brain Injury Time / 法医学杂志

Cyclin-dependent kinase 5 (CDK5) is a member of cyclin-dependent kinase family, which does not directly regulate cell cycle. Through phosphorylation of target protein, CDK5 plays an irreplaceable role in the development, reparation and degeneration of neurons. Brain injury refers to the organic injury of brain tissue caused by external force hit on the head. Owing to the stress and repair system activated by our body itself after injury, various proteins and enzymes of the brain tissues are changed quantitatively, which can be used as indicators for estimating the time of injury. This review summarizes the progress on the distribution, the activity mechanism and the physiological effects of CDK5 after brain injury and its corresponding potential served as a marker for brain injury determination.

Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior

Schizophrenia is a severe psychiatric disorder that results in a significant disability for the patient. The disorder is characterized by impairment of the adaptive orchestration of actions, a cognitive function that is mainly dependent on the prefrontal cortex. This behavioral deficit, together with cellular and neurophysiological alterations in the prefrontal cortex, as well as reduced density of GABAergic cells and aberrant oscillatory activity, all indicate structural and functional deficits of the prefrontal cortex in schizophrenia. Among the several risk factors for the development of schizophrenia, stress during the prenatal period has been identified as crucial. Thus, it is proposed that prenatal stress induces neurodevelopmental alterations in the prefrontal cortex that are expressed as cognitive impairment observed in schizophrenia. However, the precise mechanisms that link prenatal stress with the impairment of prefrontal cortex function is largely unknown. Reelin is an extracellular matrix protein involved in the development of cortical neural connectivity at embryonic stages, and in synaptic plasticity at postnatal stages. Interestingly, down-regulation of reelin expression has been associated with epigenetic changes in the reelin gene of the prefrontal cortex of schizophrenic patients. We recently showed that, similar to schizophrenic patients, prenatal stress induces down-expression of reelin associated with the methylation of its promoter in the rodent prefrontal cortex. These alterations were paralleled with altered prefrontal cortex functional connectivity and impairment in prefrontal cortex-dependent behavioral tasks. Therefore, considering molecular, cellular, physiological and behavioral evidence, we propose a unifying framework that links prenatal stress and prefrontal malfunction through epigenetic alterations of the reelin gene.

Convenção-Quadro para o Controle do Tabaco: adesão e implantação na América Latina / WHO Framework Convention on Tobacco Control: adherence and establishment in Latin America

OBJETIVO:Traçar o panorama de adesão mundial à Convenção-Quadro para o Controle do Tabaco (CQCT) e descrever a implantação das medidas preconizadas pela CQCT em países latino-americanos. MÉTODOS: Este estudo descritivo baseou-se em análise de dados secundários para determinar o status de adesão, no ano de 2015, dos países das seis regiões definidas pela Organização Mundial da Saúde (OMS) à CQCT. Depois disso, realizou-se um mapeamento da implantação, até o ano de 2012, das medidas preconizadas pela CQCT no total de Estados Partes e particularmente em 12 Estados Partes latino-americanos. Finalmente, Brasil, Chile, Colômbia, México e Venezuela foram avaliados quanto ao grau de implantação da CQCT (incipiente, intermediária e avançada). Foram consideradas neste passo medidas englobadas por quatro eixos - redução da demanda por tabaco, redução da oferta de tabaco, redução dos danos ao ambiente e à saúde das pessoas causados pelo tabaco e apoio ao abandono do tabaco. RESULTADOS: Até agosto de 2015, 180 países haviam ingressado no rol de Estados Partes da CQCT. Considerando os 126 países que enviaram relatórios de progresso global da implantação no ciclo de 2012, as medidas mais prevalentes adotadas referiam-se à proteção contra a exposição à fumaça do tabaco (83,0% para o total de países e 100% para o conjunto de países latinoamericanos). Entre os cinco países selecionados para análise detalhada, as medidas destinadas à redução da demanda e da oferta do tabaco foram as mais frequentes. As medidas relacionadas à redução de danos ao ambiente foram raras. Brasil e México apresentaram a situação mais avançada de implantação entre os países estudados. CONCLUSÕES: A América Latina apresentou uma alta proporção de Estados Partes que implantaram as medidas preconizadas pela CQCT. A heterogeneidade da situação de implantação nos cinco países selecionados sugere que as políticas de controle de tabaco são condicionadas por particularidades nacionais.

OBJECTIVE: To draw an overview of the adherence of countries around the world to the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) and to describe the establishment of WHO FCTC recommended measures in Latin American countries. METHODS: This descriptive study was based on analysis of documents and secondary data to determine the status of countries from the six WHO regions regarding adherence to the FCTC. After that, the establishment of recommended measures until the year 2012 was mapped in all States Parties and particularly in 12 Latin American States Parties. Finally, the degree to which FCTC measures had been established in Brazil, Chile, Colombia, Mexico, and Venezuela was assessed (incipient, intermediate, or advanced). This step took into consideration the measures covered by four domains - reduction in the demand for tobacco, reduction in the offer of tobacco, reduction in damage to the environment and to the health of people caused by tobacco, and support for quitting the use of tobacco. RESULTS: Until August 2015, 180 countries had joined as States Parties to the FCTC. Considering the 126 countries that submitted global progress reports in the 2012 cycle, the most prevalent measures adopted referred to the protection against exposure to tobacco smoke (83.0% for all countries and 100% for the group of Latin American countries). Among the five countries selected for detailed analysis, the measures referring to the reduction of demand and offer of tobacco were the most frequent. Measures focused on reducing environmental damage were rare. Brazil and Mexico had the most advanced FCTC status among the studied countries. CONCLUSIONS: Latin America presented a high proportion of States Parties with established FCTC recommended measures. The heterogeneity of the FCTC status in the five selected countries suggests that the implementation of tobacco control policies depends on specific aspects of each country.

Coherence of brain electrical activity: a quality of life indicator in Alzheimer’s disease?Coerência da atividade elétrica cerebral: indicador da qualidade de vida na doença de Alzheimer?

Objective To investigate the relationships between quality of life (QOL) and clinical and electroencephalogram (EEG) aspects in patients with Alzheimer’s disease (AD). Method Twenty-eight patients with mild or moderate AD, 31 with Parkinson’s disease (PD), and 27 normal controls (NC) were submitted to: CERAD neuropsychological battery, Hamilton Depression and Anxiety Rating Scales, Functional Activities Questionnaire, QOL scale for patients with AD, and quantitative EEG measures. Results AD and PD patients had similar QOL (31.0 ± 5.8; 31.7 ± 4.8, respectively), worse than that of NC (37.5 ± 6.3). AD patients had lower global interhemispheric theta coherence (0.49 ± 0.04; 0.52 ± 0.05; 0.52 ± 0.05; respectively) than PD and NC. Multiple linear regression for QOL of AD patients revealed that global interhemispheric theta coherence, and Hamilton depression scores were significant factors (coefficients; 58.2 and -0.27, respectively; R2, 0.377). Conclusion Interhemispheric coherence correlates with QOL regardless of cognitive and functional variables and seems to be a neurophysiological indicator of QOL in AD patients. .

Objetivo Investigar relações entre qualidade de vida (QV) e aspectos clínico-eletrencefalográficos (EEG) em pacientes com doença de Alzheimer (DA). Método Vinte e oito pacientes com DA, 31 com doença de Parkinson (DP) e 27 controles normais (CN) foram submetidos a avaliações neurocognitivas, escala de depressão de Hamilton e de qualidade de vida para pacientes com DA, questionário de atividades funcionais e medidas do EEG. Resultados A QV foi similar nos grupos DA e DP (31,0 ± 5,8; 31,7 ± 4,8, respectivamente), mas inferior ao CN (37,5 ± 6,3). No grupo DA houve menor coerência inter-hemisférica global teta (CIGT) do que em DP e CN (p < 0,05). Regressão múltipla linear para QV no grupo DA revelou a CIGT e a escala de Hamilton como fatores significativos (coeficientes; 58,2; -0,27, respectivamente; R2, 0,377). Conclusão A CIGT correlaciona-se com a QV independentemente de variáveis cognitivas e funcionais e parece ser um indicador neurofisológico da QV em pacientes com DA. .

Abnormal Brain Activity in Social Reward Learning in Children with Autism Spectrum Disorder: An fMRI Study

PURPOSE: We aimed to determine whether Autism Spectrum Disorder (ASD) would show neural abnormality of the social reward system using functional MRI (fMRI). MATERIALS AND METHODS: 27 ASDs and 12 typically developing controls (TDCs) participated in this study. The social reward task was developed, and all participants performed the task during fMRI scanning. RESULTS: ASDs and TDCs with a social reward learning effect were selected on the basis of behavior data. We found significant differences in brain activation between the ASDs and TDCs showing a social reward learning effect. Compared with the TDCs, the ASDs showed reduced activity in the right dorsolateral prefrontal cortex, right orbitofrontal cortex, right parietal lobe, and occipital lobe; however, they showed increased activity in the right parahippocampal gyrus and superior temporal gyrus. CONCLUSION: These findings suggest that there might be neural abnormality of the social reward learning system of ASDs. Although this study has several potential limitations, it presents novel findings in the different neural mechanisms of social reward learning in children with ASD and a possible useful biomarker of high-functioning ASDs.