Publicação
Isquémia cerebral aguda e modelação pelo sulfeto de hidrogéneo
| Resumo: | In the present study, we explored the effect of short-term exposure to hydrogen sulfide (H2S) after acute ischemia in an animal model of pMCAO. We hypothesized that H2S exposure after acute ischemic stroke modulates ischemic lesion either by an early protective effect or by promoting post-ischemic repair. To address our hypothesis we exposed rats to H2S after pMCAO and measured functional outcome and infarct size in vivo and post-mortem. We identified underlying markers of cytoprotection and repair. Finally, we compared brain imaging with immunohistochemical data to look for early imaging features of ischemic tissue damage that may relate to functional outcome. H2S exposure after pMCAO improved functional outcome and decreased infarct size and the expression of cell death. H2S may act very early in the ischemic process, since there were lower levels of acute injury-related markers at 24h without enhancement of repair-associated markers for vasculogenesis, angiogenesis or synaptogenesis at day 14. Significant benefit is likely to occur before major tissue damage develop and includes modulation of NOX-4, a major enzyme generator of reactive oxygen species (ROS) and endothelial dysfunction, as well as by vasomodulation of intralesional microcirculation, since intralesional CBF assessed by PWI MRI improved in rats exposed to H2S. Given that H2S limits brain damage after experimental ischemic stroke, hydrogen sulfide donors may play a role as new drugs in the context of acute ischemic stroke. |
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| Autores principais: | Henriques, Maria Isabel Santos Lestro |
| Assunto: | Isquemia encefálica Artéria cerebral média Sulfeto de hidrogénio Cérebro Neurologia Teses de doutoramento - 2015 |
| Ano: | 2015 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | português |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | In the present study, we explored the effect of short-term exposure to hydrogen sulfide (H2S) after acute ischemia in an animal model of pMCAO. We hypothesized that H2S exposure after acute ischemic stroke modulates ischemic lesion either by an early protective effect or by promoting post-ischemic repair. To address our hypothesis we exposed rats to H2S after pMCAO and measured functional outcome and infarct size in vivo and post-mortem. We identified underlying markers of cytoprotection and repair. Finally, we compared brain imaging with immunohistochemical data to look for early imaging features of ischemic tissue damage that may relate to functional outcome. H2S exposure after pMCAO improved functional outcome and decreased infarct size and the expression of cell death. H2S may act very early in the ischemic process, since there were lower levels of acute injury-related markers at 24h without enhancement of repair-associated markers for vasculogenesis, angiogenesis or synaptogenesis at day 14. Significant benefit is likely to occur before major tissue damage develop and includes modulation of NOX-4, a major enzyme generator of reactive oxygen species (ROS) and endothelial dysfunction, as well as by vasomodulation of intralesional microcirculation, since intralesional CBF assessed by PWI MRI improved in rats exposed to H2S. Given that H2S limits brain damage after experimental ischemic stroke, hydrogen sulfide donors may play a role as new drugs in the context of acute ischemic stroke. |
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