Schwalm Mágada T, Pasquali Matheus, Miguel Samantha P, Dos Santos João Paulo A, Vuolo Francieli, Comim Clarissa M, Petronilho Fabrícia, Quevedo João, Gelain Daniel P, Moreira José Cláudio F, Ritter Cristiane, Dal-Pizzol Felipe
Laboratório de Fisiopatologia Experimental and Instituto Nacional de Ciência e Técnologia Translacional em Medicina, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Avenida Universitária, 1105, Criciúma, 88006-000, Santa Catarina, Brazil.
Mol Neurobiol. 2014 Feb;49(1):380-5. doi: 10.1007/s12035-013-8526-3. Epub 2013 Aug 30.
Survivors from sepsis present long-term cognitive deficits and some of these alterations resemble the pathophysiological mechanisms of neurodegenerative diseases. For this reason, we analyzed beta-amyloid peptide (Aβ) and synaptophysin levels in the brain of rats that survived from sepsis and their relation to cognitive dysfunction and to acute brain inflammation. Sepsis was induced in rats by cecal ligation and puncture, and 30 days after surgery, the hippocampus and prefrontal cortex were isolated just after cognitive evaluation by the inhibitory avoidance test. The immunocontent of Aβ and synaptophysin were analyzed by Western blot analysis. Aβ increased and synaptophysin decreased in septic animals both in the hippocampus and prefrontal cortex concurrent with the presence of cognitive deficits. Prefrontal levels of synaptophysin correlated to the performance in the inhibitory avoidance. Two different treatments known to decrease brain inflammation and oxidative stress when administered at the acute phase of sepsis decreased Aβ levels both in the prefrontal cortex and hippocampus, increased synaptophysin levels only in the prefrontal cortex, and improved cognitive deficit in sepsis-survivor animals. In conclusion, we demonstrated that brain from sepsis-survivor animals presented an increase in Aβ content and a decrease in synaptophysin levels and cognitive impairment. These alterations can be prevented by treatments aimed to decrease acute brain inflammation and oxidative stress.
脓毒症幸存者存在长期认知缺陷，其中一些改变类似于神经退行性疾病的病理生理机制。因此，我们分析了脓毒症存活大鼠大脑中的β-淀粉样肽（Aβ）和突触素水平，以及它们与认知功能障碍和急性脑炎症的关系。通过盲肠结扎和穿刺诱导大鼠发生脓毒症，术后30天，在通过抑制性回避试验进行认知评估后，分离海马体和前额叶皮质。通过蛋白质免疫印迹分析来分析Aβ和突触素的免疫含量。脓毒症动物的海马体和前额叶皮质中，Aβ增加而突触素减少，同时存在认知缺陷。前额叶皮质中突触素水平与抑制性回避试验中的表现相关。在脓毒症急性期给予两种已知可减轻脑炎症和氧化应激的不同治疗，可降低前额叶皮质和海马体中的Aβ水平，仅在前额叶皮质中增加突触素水平，并改善脓毒症存活动物的认知缺陷。总之，我们证明脓毒症存活动物大脑中的Aβ含量增加、突触素水平降低以及存在认知障碍。这些改变可以通过旨在减轻急性脑炎症和氧化应激的治疗来预防。
