Estudo neuropatológico e neuroquímica da inflamação no hipocampo de pacientes com epilepsia do lobo temporal associada à esclerose mesial
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Data
2009-06-24
Autores
Varella, Pedro Paulo Vasconcellos [UNIFESP]
Orientadores
Naffah-Mazzacoratti, Maria da Graca [UNIFESP]
Tipo
Tese de doutorado
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Objetivos: Estudar a existência de correlação linear entre a intensidade do sinal na IRM do hipocampo em FLAIR na ELT com EH e a concentração de GLU, NO, IL1β e TNFα. Em outro enfoque, objetivamos comparar as concentrações hipocampais destes mediadores entre os pacientes com ELT e EH e controles obtidos de autópsia. Metodologia: Estudamos 29 pacientes com ELT por EH e 20 indivíduos controles (10 autópsia e 10 controles de IRM). O sinal na IRM foi medido em FLAIR (Leonardo, Syngo MR 2004A Siemens Medical Solutions) tanto para pacientes como para controles. As concentrações de GLU formam obtidas por cromatografia líquida (HPLC), a de IL1β e TNFα foram obtidas por ELISA (Kit BD Opteia) e a de NO foi aferida pelo equipamento NOATM 280, Sievers Instruments. Os dados foram avaliados utilizando-se os testes t de Student para a comparações de concentrações de mediadores nos diferentes tecidos e o teste exato de Fisher, de Kolmogorov-Smirnov, de Levene para a avaliação da correlação linear de Pearson entre as variáveis. Resultados: Quanto avaliamos as concentrações dos diferentes mediadores em tecido com EH e controle observamos aumento da concentração de IL1β e TNFα e redução do GLU e GABA na EH, sem alterações significativas do NO. Houve correlação linear positiva entre as concentrações de NO, e hipersinal em FLAIR tanto na cabeça, corpo e cauda do hipocampo. A citocina IL1β mostrou correlação linear positiva com o sinal em FLAIR na cauda hipocampal. Além disso, houve correlação linear inversa entre o sinal de FLAIR e a concentração de GLU no hipocampo de pacientes com EH. Conclusão: Esses dados sugerem haver correlação entre liberação de GLU e intensidade de sinal em FLAIR na IRM. Por outro lado a correlação positiva entre NO e IL1β e sinal em FLAIR também sugere associação com o fenômeno inflamatório e quantidade de água no hipocampo. Desta forma, concluímos que na EH há inflamação e excitotoxicidade, mesmo nas fases crônicas da síndrome, flagradas pelas alterações das concentrações de IL1β, TNFα e GLU e NO. Estas alterações podem estar correcionadas com o hipersinal da IRM em FLAIR
Purpose: To study the existence of linear correlation between the intensity of the MRI T2 signal in the hippocampus of patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) and the concentration of GLU, NO, TNFα and IL1β. In another approach, we aimed to compare the hippocampal concentrations of these mediators between patients with TLE with HE and control subjects, obtained from autopsy. Methods: We studied 29 patients with TLE with HS and 20 control subjects (10 autopsy and 10 controls for MRI). The signal was measured on MRI in T2 (Leonardo, 2004a MR Syngo Siemens Medical Solutions) for both patients and for controls. The concentrations of GLU are obtained by liquid chromatography (HPLC), the IL1β and TNFα concentration were obtained by ELISA (BD Opt Kit) and the NO level was measured by the equipment NOATM 280, Sievers Instruments. Data were evaluated using the Student t test for the comparison of mediator’s concentrations in the hippocampus of control and patients with HS and the Fisher exact test, the Kolmogorov-Smirnov, Levene was employed for the evaluation of the Pearson's linear correlation between variables.Results: The evaluation of the inflammatory mediator’s concentration in tissues with HS and controls showed increased concentration of IL1β and TNFα as well as reduction of GLU and GABA in HS, without significant changes of NO levels. A positive linear correlation between NO levels and signal on T2 in the head, body and tail of hippocampus were also found. The cytokine IL1β levels showed positive 160linear correlation with the MRI T2 signal with the tail of the hippocampus. Moreover, an inverse linear correlation between the T2 MRI signal and the concentration of GLU in the hippocampus of patients with HE was also detected. Conclusion: These data suggest a correlation between the increased release of GLU and the intensity of T2 MRI signal. Furthermore the positive correlation between NO and IL1β and T2 MRI signal suggests an association between hipersignal, inflammation and amount of water in the hippocampus of these patients. Thus, we conclude that there is inflammation and excitotoxicity in TLE with HS, even in chronic stages of this syndrome, visualized by changes in the concentrations of IL1β, TNFα, GLU and NO. These changes could be related to the hypersignal on T2 MRI.
Purpose: To study the existence of linear correlation between the intensity of the MRI T2 signal in the hippocampus of patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) and the concentration of GLU, NO, TNFα and IL1β. In another approach, we aimed to compare the hippocampal concentrations of these mediators between patients with TLE with HE and control subjects, obtained from autopsy. Methods: We studied 29 patients with TLE with HS and 20 control subjects (10 autopsy and 10 controls for MRI). The signal was measured on MRI in T2 (Leonardo, 2004a MR Syngo Siemens Medical Solutions) for both patients and for controls. The concentrations of GLU are obtained by liquid chromatography (HPLC), the IL1β and TNFα concentration were obtained by ELISA (BD Opt Kit) and the NO level was measured by the equipment NOATM 280, Sievers Instruments. Data were evaluated using the Student t test for the comparison of mediator’s concentrations in the hippocampus of control and patients with HS and the Fisher exact test, the Kolmogorov-Smirnov, Levene was employed for the evaluation of the Pearson's linear correlation between variables.Results: The evaluation of the inflammatory mediator’s concentration in tissues with HS and controls showed increased concentration of IL1β and TNFα as well as reduction of GLU and GABA in HS, without significant changes of NO levels. A positive linear correlation between NO levels and signal on T2 in the head, body and tail of hippocampus were also found. The cytokine IL1β levels showed positive 160linear correlation with the MRI T2 signal with the tail of the hippocampus. Moreover, an inverse linear correlation between the T2 MRI signal and the concentration of GLU in the hippocampus of patients with HE was also detected. Conclusion: These data suggest a correlation between the increased release of GLU and the intensity of T2 MRI signal. Furthermore the positive correlation between NO and IL1β and T2 MRI signal suggests an association between hipersignal, inflammation and amount of water in the hippocampus of these patients. Thus, we conclude that there is inflammation and excitotoxicity in TLE with HS, even in chronic stages of this syndrome, visualized by changes in the concentrations of IL1β, TNFα, GLU and NO. These changes could be related to the hypersignal on T2 MRI.
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Citação
VARELLA, Pedro Paulo Vasconcellos. Estudo neuropatológico e neuroquímica da inflamação no hipocampo de pacientes com epilepsia do lobo temporal associada à esclerose mesial. 2009. Tese (Doutorado) - Universidade Federal de São Paulo (UNIFESP), São Paulo, 2009.