Increased Metallothionein I/II Expression in Patients with Temporal Lobe Epilepsy

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) and patients with TLE associated with tumor or dysplasia (TLE-TD) were evaluated for expression of MT-I/II, for the vesicular zinc levels, and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis, microgliosis and reduced neuronal population. In TLE-TD, the same changes were observed, except that were mainly confined to fascia dentata. Increased vesicular zinc was observed only in the inner molecular layer of MTLE patients, when compared to control cases. Correlation and linear regression analyses indicated an association between increased MT-I/II and increased astrogliosis in TLE. MT-I/II levels did not correlate with any clinical variables, but MTLE patients with secondary generalized seizures (SGS) had less MT-I/II than MTLE patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from TLE patients and our data suggest that it is associated with astrogliosis and may be associated with different seizure spread patterns.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2005/56447-7, 2009/53447-7, 2008/52657-5]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Níveis diferentes de MT-I/II entre pacientes com MTLE com ou sem crise generalizada: os níveis hipocampais de MT-I/II afetam o alastramento das crises, ou o alastramento das crises promove expressão diferencial de MT-I/II?

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) were evaluated for expression of MT-I/II and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis and reduced neuronal population. MT-I/II levels did not correlate with any clinical variables, but patients with secondary generalized seizures (SGS) had less MT-I/II than patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from MTLE patients and our data suggest that it may be associated with different seizure spread patterns

Editorial

Neste primeiro número de 2019, a revista Archives of Health Sciences, com diagramação reformulada,  presenta uma nova coleção de dezessete artigos de várias disciplinas da área da saúde. No volume, cujos artigos contam com autores brasileiros de todas as regiões do país, há um foco em estudos originais. Como exemplos desses artigos selecionados pela equipe editorial, podem ser mencionados estudos que indicam a necessidade de reforço e de geração de estratégias para a prevenção de doenças de impacto social e epidemiológico significativos (tais como a sífilis gestacional e congênita1 e hipertensão arterial em crianças2) e estudos com pacientes idosos, um que aponta efeitos benéficos da terapia de Pilates3 e outro que avalia o risco de queda e o medo de cair4. Além desses, é possível encontrar ainda estudos com um foco em metodologia, como a análise de índices prognósticos de sobrevivência, em pacientes queimados, que demonstra a capacidade de discriminação dos mesmos5. Somados aos estudos acima mencionados, também foram selecionadas revisões da literatura, dentre as quais se encontram um estudo na área da imunologia sobre o sistema do complemento, que descreve um apanhado interessante sobre doenças associadas à deficiência desse sistema6 e outro que mostra o importante efeito de terapias complementares e lúdicas com uso da arte, no cuidado de enfermagem em saúde mental7. Adicionalmente, também foram selecionados relatos de casos, como o de pacientes com hipertensão pulmonar, inicialmente considerada idiopática, apresentando o processo de avaliação e reclassificação do diagnóstico para hipertensão pulmonar secundária a esclerose sistêmica8. Aproveito para destacar e agradecer o excelente trabalho da equipe de editores e revisores, que ao longo dos últimos meses se dedicaram de forma exaustiva para o sucesso deste volume. Desejo uma excelente leitura

Correction: Increased Metallothionein I/II Expression in Patients with Temporal Lobe Epilepsy.

[This corrects the article DOI: 10.1371/journal.pone.0044709.]

Mesial temporal lobe epilepsy: Clinical and neuropathologic findings of familial and sporadic forms

To evaluate the clinical and hippocampal histological features of patients with mesial temporal lobe epilepsy (MTLE) in both familial (FMTLE) and sporadic (SMTLE) forms. Patients with FMTLE (n = 20) and SMTLE (n = 39) who underwent surgical treatment for refractory seizures were studied at the University of Sao Paulo School of Medicine at Ribeirao Preto. FMTLE was defined when at least two individuals in a family had clinical diagnosis of MTLE. Hippocampi from all patients were processed for Nissl/HE and Timm's stainings. Both groups were compared for clinical variables, hippocampal cell densities, and intensity of supragranular mossy fiber staining. There were no significant differences between FMTLE and SMTLE groups in the following: age at the surgery, age of first usual epileptic seizure, history of initial precipitating injury (IPI), age of IPI, latent period, ictal and interictal video-EEG patterns, presence of hippocampal atrophy and signal changes at MRI, and postoperative outcome. In addition, no differences were found in cell densities in hippocampal cornu ammonis subfields (CA1, CA2, CA3, CA4), fascia dentata, polymorphic region, subiculum, prosubiculum, and presubiculum. However, patients with SMTLE had greater intensity of mossy fiber Timm's staining in the fascia dentata-inner molecular layer (p < 0.05). Patients with intractable FMTLE present a clinical profile and most histological findings comparable to patients with SMTLE. Interestingly, mossy fiber sprouting was less pronounced in patients with FMTLE, suggesting that, when compared to SMTLE, patients with FMTLE respond differently to plastic changes plausibly induced by cell loss, neuronal deafferentation, or epileptic seizures4961046105

Myocardial Infarction Area Quantification using High-Resolution SPECT Images in Rats

FUNDAMENTO: Técnicas de imageamento in vivo permitem avaliar sequencialmente a morfologia e a função dos órgãos em diversos modelos experimentais. Desenvolvemos um dispositivo de adaptação de uma gama-câmara clínica para obter imagens tomográficas por emissão de fótons singulares (SPECT) de alta resolução, baseado em colimador pinhole. OBJETIVO: Determinar a acurácia desse sistema na quantificação da área de infarto miocárdico em ratos. MÉTODOS: Treze ratos Wistar machos (250 g) foram submetidos a infarto do miocárdio por oclusão da artéria coronária esquerda. Após 4 semanas, foram adquiridas imagens tomográficas com o sistema desenvolvido, 1,5 hora após a injeção endovenosa de 555MBq de 99mTc-Sestamibi. Na reconstrução tomográfica, utilizamos software especialmente desenvolvido baseado no algoritmo de Máxima Verossimilhança. Comparamos as médias e analisamos a correlação entre a extensão dos defeitos perfusionais detectados pela cintilografia e a extensão da fibrose miocárdica avaliada pela histologia. RESULTADOS: As imagens apresentaram ótima relação órgão-alvo/fundo, com apropriada visualização das paredes e da cavidade do ventrículo esquerdo. Todos os animais exibindo áreas de infarto foram corretamente identificados pelas imagens de perfusão. Não houve diferença entre a área do infarto medida pelo SPECT (21,1 ± 21,2%) e pela histologia (21,7 ± 22,0%; p = 0,45), obtendo forte correlação entre os valores da área de infarto mensurada pelos dois métodos (r = 0,99; p < 0,0001). CONCLUSÃO: O sistema desenvolvido apresentou resolução espacial adequada e elevada acurácia para detecção e quantificação das áreas de infarto miocárdico, sendo uma opção de baixo custo e grande versatilidade na obtenção de imagens em SPECT de alta resolução de órgãos de pequenos roedores

HLA-DR immunopositive area in hippocampal subfields of Ctrl, MTLE and TLE-TD groups.

<p>Compared to Ctrl (white boxplots), TLE groups had increased HLA-DR immunoreactivity (showed as percentage of immunopositive area) in outer molecular layer (OML), granule cell layer (GCL), CA4, and CA1 subfields (p<0.001). MTLE (dark gray boxplots) had increased HLA-DR immunoreactivity in inner molecular layer (IML), subgranule zone (SGZ), hilus, CA3, CA2, prosubiculum (PRO) and subiculum (SUB) (p<0.01). In IML, MTLE also presented increased HLA-DR immunoreactivity when compared to TLE-TD (p<0.001). The * indicate difference from Ctrl and ^# difference from TLE-TD.</p

Representative images of MT-I/II staining in several hippocampal subfields.

<p>Almost all stained cells have astrocyte morphology (indicated by small arrows in A–F), while neurons remained unstained (white cells pointed by large arrows in B). Only in few cases from Ctrl (E and F) and in one region of one case of TLE were observed cells with neuron morphology (large arrows in E and F). No stained neuron presented the strong staining of astrocytes. In Ctrl, neuropil presented a weak staining (indicated by black circle in F). In TLE the neuropil staining level was heterogeneous, as can be seen in CA1 sections depicted in C and D (indicated by white circles). The representative images shown are from the <i>fascia dentate</i> (A), <i>subiculum</i> (B and E), CA1 (C and D) and <i>hilus</i> (F) of Ctrl (E and F) and TLE cases (A–D). Bar in F indicates 100 micrometers.</p