Neurosciences and Behavioral Sciences

Como postulado inicialmente na década de 50 por Hebb (1), a associação de diferentes padrões de atividade neuronal é capaz de promover mudanças específicas na eficiência da transmissão sináptica que compõe uma circuitaria neural, determinando uma plasticidade sináptica. Tais mudanças levam a alterações no processamento de informações de caráter sensorial, motor, emocional, cognitivo ou motivacional, podendo gerar novos modos de comportamento, e assim propiciar uma plasticidade comportamental. Acredita-se hoje que estes sejam importantes mecanismos celulares envolvidos em diversos comportamentos adaptativos como a formação de memórias e formação de hábitos, assim como de comportamentos patológicos, vício em drogas, epilepsia e transtornos neuropsiquiátricos. Além disso, inúmeras evidências se 1. A ordem dos quatro primeiros autores foi colocada de maneira alfabética (pelo sobrenome), pois todos estes autores tiveram igual participação na redação deste capítulo. acumulam indicando modificações eletrofisiológicas e moleculares que correlacionam plasticidade sináptica e plasticidade comportamental.

Assessing interindividual variability of brain activation is of practical importance to the use of functional magnetic resonance imaging (fMRI) in the clinical context. The main objective of this study is to analyze the variability of the oculomotor system through horizontal optokinetic, pursuit and saccadic eye movement stimulations by means of fMRI. We found significant activation of many cortical and subcortical structures. The frequency of activation demonstrates a high variability between subjects. However, the most frequent activation regions were located in frontal areas and in regions comprising the middle temporal and medial superior temporal areas. Our study allowed the characterization of the most frequently involved foci in optokinetic stimulation, pursuit and saccadic eye movement tasks. The combination of these tasks constitutes a suitable tool for mapping major areas involved in the oculomotor system.

This study compared MRI cerebral volumes and Neuronal-Nuclei (NeuN) cell densities in pediatric epilepsy surgery patients with cortical dysplasia (CD; n = 25) and hemimegalencephaly (HME; n = 14). Our purpose was to deduce possible mechanisms of pathogenesis and epileptogenesis based on an understanding of normal developmental corticoneurogenesis. We used MRI to measured cerebral hemisphere volumes, and NeuN staining to determine grey and white matter cell densities and cell sizes in the molecular layer, grey, and white matter. CD and HME surgical cases were compared with autopsy or non-CD cases (n = 20). Total MRI brain volumes were similar between non-CD, CD, and HME cases. However, in HME patients, the affected cerebral hemisphere was larger and the nonaffected side smaller than non-CD cases. Compared with autopsy cases, NeuN cell densities and cell sizes in CD and HME patients were increased in the molecular layer, upper grey matter, and white matter. In CD and HME cases, total ...

Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and affects 40% of the patients. Seizures arising from the mesial temporal lobe structures (i.e., amygdala and hippocampus) are common, whereas neocortical seizures are rare. In recent years, many studies aimed to identify the pattern of gene expression of neurotransmitters involved in molecular mechanisms of epilepsy. We used real-time PCR to quantify the expression of GABA A (subunits a1, b1, b2) and NMDA (subunits NR1, NR2A, and NR2B) receptor genes in amygdalae of 27 patients with TLE and 14 amygdalae from autopsy controls. The NR1 subunit was increased in patients with epilepsy when compared with controls. No differences were found in expression of NMDA subunits NR2A and NR2B or in a1, b1, and b2 subunits of GABA A receptors. Our results suggest that the NR1 subunit of NMDA receptors is involved in the amygdala hyperexcitability in some of the patients with TLE. V V C 2010 Wiley Periodicals, Inc.

Introdução: A estruturação do ensino médico nas escolas médicas brasileiras ao longo do século XX sofreu grande influência das idéias de Abrahan Flexner, educador americano que julgava ser o ensino indissociável da pesquisa. Para tanto, o ensino deveria ser desenvolvido em escolas com adequada infra-estrutura de hospitais e laboratórios para o estudo das doenças. Este trabalho tem por objetivo apresentar o cenário atual da pesquisa em epilepsia no âmbito do ensino de graduação e pós-graduação das escolas médicas brasileiras. Material e métodos: Busca a análise de informações obtidas em bancos de dados governamentais (MEC e CAPES), de declarações de diretorias de instituições representativas dos órgãos médicos (AMB e CFM) além de informações obtidas no Encontro Nacional de Pós-Graduação em Medicina. Resultados e discussão: O número crescente de escolas médicas nos últimos anos, associado a um ainda questionável sistema de avaliação, tem contribuído para que muitas escolas se estabeleçam sem o perfil adequado para a pesquisa em neurologia. Assim, a pesquisa em epilepsia brasileira, no âmbito da graduação, esta praticamente restrita a instituições vinculadas às principais Universidades Federais, Estaduais (principalmente as Estaduais Paulistas), e algumas do sistemas das PUCs. Nestas instituições observa-se a presença de Professores/Pesquisadores que ministram aulas nos cursos de medicina, mas que também atuam em Programas de Pós-Graduação. Em contraste com a graduação, a plena autonomia conferida ao sistema de avaliação da CAPES para o descredenciamento de programas com avaliação insuficiente, tem permitido uma melhora significativa na qualidade dos Programas de Pós-Graduação.

This study was designed to determine whether hippocampal neuronal AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and NMDA (N-methyl-D-aspartate) mRNA levels were differentially increased in temporal lobe epilepsy patients compared with those measured in control tissue from non-seizure autopsies. Hippocampi from hippocampal sclerosis patients (n ϭ 28) and temporal mass lesion cases (n ϭ 12) were compared with those from the autopsies (n ϭ 4), and studied for AMPA GluR1-3 and NMDAR1-2 mRNAs using semi-quantitative in situ hybridization, along with fascia dentata and Ammon's horn neuron densities. Compared with the autopsies, and without correction for neuron counts, the mass lesion cases with neuron densities similar to autopsies showed: (i) significantly increased NMDAR2 hybridization densities for fascia dentata granule cells; (ii) increased AMPA GluR3 mRNA densities for Ammon's horn pyramids; and (iii) similar or numerically increased mRNAs for all other subunits and hippocampal subfields. Compared with the autopsies, hippocampal sclerosis cases with decreased neuron densities showed: (i) significantly decreased AMPA GluR1-2 and NMDAR1-2 hybridization densities for Abbreviations: AMPA ϭ α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid; GluR ϭ glutamate receptor; non-HS ϭ without hippocampal sclerosis; NMDA ϭ N-methyl-D-aspartate; NMDAR ϭ NMDA receptor; SSC ϭ standard saline citrate; STS ϭ sodium thiosulphate

Background: Better treatments for schizophrenia are urgently needed. The therapeutic use of the nitric oxide (NO)-donor sodium nitroprusside (SNP) in patients with schizophrenia has shown promising results. The role of NO in schizophrenia is still unclear, and NO modulation is unexplored in ketamine (KET) animal models to date. In the present study, we compared the behavioral effects of pre-and post-treatment with SNP, glyceryl trinitrate (GTN), and methylene blue (MB) in the acute KET animal model of schizophrenia. The present study was designed to test whether acute SNP, GTN, and MB treatment taken after (therapeutic effect) or before (preventive effect) a single KET injection would influence the behavior of rats in the sucrose preference test, object recognition task and open field.

Changes in the subunit stoichiometry of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) alters its channel properties, and may enhance or reduce neuronal excitability in temporal lobe epilepsy patients. This study determined whether hippocampal NMDA receptor subunit mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsy cases. Hippocampal sclerosis (HS; n ‫؍‬ 16), non-HS (n ‫؍‬ 10), and autopsy hippocampi (n ‫؍‬ 9) were studied for NMDAR1 (NR1) and NR2A-D mRNA levels by using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, non-HS and HS patients showed increased NR2A and NR2B hybridization densities per dentate granule cell. Furthermore, non-HS hippocampi showed increased NR1 and NR2B mRNA levels per CA2/3 pyramidal neuron compared with autopsy cases. HS patients, by contrast, showed decreased NR2A hybridization densities per CA2/3 pyramidal neuron compared with non-HS and autopsy cases. These findings indicate that chronic temporal lobe seizures are associated with differential changes in hippocampal NR1 and NR2A-D hybridization densities that vary by subfield and clinical-pathological category. In temporal lobe epilepsy patients, these findings support the hypothesis that in dentate granule cells NMDA receptors are increased, and excitatory postsynaptic potentials should be strongly NMDA mediated compared with nonseizure autopsies. HS patients, by comparison, showed decreased pyramidal neuron NR2A mRNA levels, and this suggests that NMDA-mediated pyramidal neuron responses should be reduced in HS patients compared with non-HS cases.

Purpose: We sought to analyze the contralateral volumes of the temporal pole, posterior segment of the temporal lobe, amygdala, hippocampus, and parahippocampal gyrus in patients with temporal lobe epilepsy (TLE) due to histologically proven mesial temporal lobe sclerosis (MTLS), seizure free for ≥4 years of postsurgical follow-up.

Purpose: We analyze a series of patients with mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) submitted to presurgical investigation with scalp sphenoidal, followed by foramen ovale electrodes (FO), and, when necessary, with depth temporal electrodes. We sought to evaluate the clinical utility of FO in patients with MTLE-HS.

Background: Neurocysticercosis is a major cause of epilepsy in developing countries and is endemic in Brazil. To test the hypothesis that the aetiological profile of patients with intractable epilepsy in Brazil includes neurocysticercosis, we conducted a cross sectional study investigating the aetiology of intractable epilepsy. Methods: A total of 512 patients evaluated at the outpatient clinic for intractable epilepsy at the Ribeirão Preto School of Medicine were included in the survey. Medical intractability was determined on the basis of seizure incidence and severity, and response to appropriate epilepsy management. Neuroimaging included brain CT with non-contrasted and contrasted phases and high resolution MRI. Patients were divided into neurocysticercosis and non-neurocysticercosis groups according to previous diagnostic criteria. Results: The most common epileptogenic lesions were mesial temporal sclerosis (MTS; 56.0%), malformations of cortical development (12.1%), and brain tumours (9.9%). Neuroimaging was normal in 8.7% of patients. Calcifications were found in 27% of patients and were significantly more common in patients with MTS than in those without MTS (p,0.001). Isolated neurocysticercosis was found in only eight patients (1.56%). Conclusions: These data suggest that neurocysticercosis is an uncommon cause of intractable epilepsy, even in an endemic region such as Brazil, and that it may only represent a coexistent pathology. However, an analysis of our findings reveals that neurocysticercosis was more common in patients with MTS. This finding could suggest either that there is a cause-effect relationship between MTS and neurocysticercosis, or that MTS and neurocysticercosis co-vary with a missing variable, such as socio-economic status.