ESTUDIO COMPARADO DEL ESTRÉS NITROSATIVO EN CEREBELO VERSUS TRONCO ENCEFÁLICO TRAS ISQUEMIA GLOBAL POR PARADA CARDIACA
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2016-10-26
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Jaén: Universidad de Jaén
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[ES]El estudio y conocimiento de las enfermedades isquémicas es de vital importancia, ya que estas patologías suponen la segunda causa de mortalidad y morbilidad en España. El sistema nervioso central (SNC) es una de las regiones más vulnerables ante la isquemia, si bien se ha demostrado por neuroimagen que el daño producido no es homogéneo a lo largo del encéfalo, existiendo regiones altamente susceptibles, cómo el cerebelo, y otras que no lo son tanto cómo el tronco encefálico. Entre las causas responsables del daño isquémico, se sabe que juegan un importante papel las especies reactivas de oxígeno y nitrógeno. En concreto, la producción de una excesiva cantidad de óxido nítrico (NO) provoca su acumulación en las células, y la formación de especies reactivas muy tóxicas como el peroxinitrito (ONOO-) que impactan y dañan a las moléculas biológicas. Por ello, se ha llevado a cabo un estudio comparado del sistema productor de NO y de los impactos nitrosativos causados a proteínas, en cerebelo y tronco encefálico; ello ha permitido elucidar la relación del sistema productor de NOcon la distinta susceptibilidad ante el daño isquémicoque presentan ambas regiones. Los resultados obtenidos indican que la isquemia provoca en las regiones estudiadas: (i) un aumento de actividad de las enzimas productoras de NO (óxido nítrico sintasas: NOS) evidenciado por un mayor marcaje para la NADPH-d; (ii) un incremento de los niveles de nitratos, nitritos y compuestos S-nitrosos (NOx), analizados mediante quimioluminiscencia (NOATM); y (iii) un aumento de los impactos nitrosativos puestos de manifiesto mediante el uso de un anticuerpo anti-nitrotirosina(N-Tyr). Además, estos cambios del sistema NO/NOS provocados por la isquemia fueron más significativos en cerebelo que en tronco encefálico. En conclusión, los resultados obtenidos confirman la hipótesis planteada, en cuanto a la influencia del sistema NO/NOS en la diferente susceptibilidad frente a isquemia de ambas regiones del encéfalo, abriendo paso a nuevos abordajes terapéuticos frente a esta incapacitante enfermedad.
[EN]The study and knowledge about the ischemic disease is a health key matter, given that this pathology represents the second cause of mortality and morbidity in Spain. The central nervous system (CNS) is one of the ischemic more vulnerable regionof the organism; however,as it was demonstrated by neuroimage, the ischemic injury is not homogeneousthroughout the brain, and there is some highly susceptible regions, as the cerebellum, and others much more resistant as the brain stem. During an ischemic insult it takes place an excessive production of nitric oxide (NO) that it is accumulated in cells inducing the formation of highly toxic reactive species such as peroxynitrite (ONOO-); this and other NO-derived reactive species impact and damage the biological molecules. In this light, it has been proposed a study of the NO production system as well as the protein nitrosative impacts in two regions of the brain: the cerebellum and the brainstem. Thestudy has allowed elucidating the relationship between the NO/NOS producing system and the different susceptibility to ischemic injury of both brain regions. The results indicate that cardiac arrest ischemia causes in the two brain studiedregionsthe following effects: (i) an activity increase of the producing NO enzymes (nitric oxide synthases: NOS) evidenced by NADPH-d-staining increased; (ii) an increase in the levels of nitrate, nitrite and S-nitrose compounds (NOx), analyzed by chemiluminescence (NOATM); and (iii) an increase of the protein nitrosative impacts analyzed by an anti-nitrotyrosine(N-Tyr) antibody. Finally, it was also foundthat these ischemic-changes were more significant in cerebellum than in the brain stem. In conclusion, the results presented here confirm that the influence of the NO/NOS system in the different susceptibility to ischemia of both brain regions, making way for new therapeutic approaches against this disabling disease.
[EN]The study and knowledge about the ischemic disease is a health key matter, given that this pathology represents the second cause of mortality and morbidity in Spain. The central nervous system (CNS) is one of the ischemic more vulnerable regionof the organism; however,as it was demonstrated by neuroimage, the ischemic injury is not homogeneousthroughout the brain, and there is some highly susceptible regions, as the cerebellum, and others much more resistant as the brain stem. During an ischemic insult it takes place an excessive production of nitric oxide (NO) that it is accumulated in cells inducing the formation of highly toxic reactive species such as peroxynitrite (ONOO-); this and other NO-derived reactive species impact and damage the biological molecules. In this light, it has been proposed a study of the NO production system as well as the protein nitrosative impacts in two regions of the brain: the cerebellum and the brainstem. Thestudy has allowed elucidating the relationship between the NO/NOS producing system and the different susceptibility to ischemic injury of both brain regions. The results indicate that cardiac arrest ischemia causes in the two brain studiedregionsthe following effects: (i) an activity increase of the producing NO enzymes (nitric oxide synthases: NOS) evidenced by NADPH-d-staining increased; (ii) an increase in the levels of nitrate, nitrite and S-nitrose compounds (NOx), analyzed by chemiluminescence (NOATM); and (iii) an increase of the protein nitrosative impacts analyzed by an anti-nitrotyrosine(N-Tyr) antibody. Finally, it was also foundthat these ischemic-changes were more significant in cerebellum than in the brain stem. In conclusion, the results presented here confirm that the influence of the NO/NOS system in the different susceptibility to ischemia of both brain regions, making way for new therapeutic approaches against this disabling disease.