The role of microglia activation in the development of sepsis-induced long-term cognitive impairment.
Oxidative stress and inflammation is likely to be a major step in the development of sepsis-associated encephalopathy (SAE) and long-term cognitive impairment. To date, it is not known whether brain inflammation and oxidative damage are a direct consequence of systemic inflammation or whether these events are driven by brain resident cells, such as microglia. Therefore, the aim of this study is to evaluate the effect of minocycline on behavioral and neuroinflammatory parameters in rats submitted to sepsis. Male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP). The animals were divided into sham-operated (Sham+control), sham-operated plus minocycline (sham+MIN), CLP (CLP+control) and CLP plus minocycline (CLP+MIN) (100 μg/kg, administered as a single intracerebroventricular (ICV) injection). Some animals were killed 24h after surgery to assess the breakdown of the blood brain barrier, cytokine levels, oxidative damage to lipids (TBARS) and proteins in the hippocampus. Some animals were allowed to recover for 10 days when step-down inhibitory avoidance and open-field tasks were performed. Treatment with minocycline prevented an increase in markers of oxidative damage and inflammation in the hippocampus after sepsis. This was associated with an improvement in long-term cognitive performance. In conclusion, we demonstrated that the inhibition of the microglia by an ICV injection of minocycline was able to decrease acute brain oxidative damage and inflammation as well as long-term cognitive impairment in sepsis survivors.
['Michels|Monique|M|', 'Vieira|Andriele S|AS|', 'Vuolo|Francieli|F|', 'Zapelini|Hugo Galvane|HG|', 'Mendonça|Bruna|B|', 'Mina|Francielle|F|', 'Dominguini|Diogo|D|', 'Steckert|Amanda|A|', 'Schuck|Patrícia Fernanda|PF|', 'Quevedo|João|J|', 'Petronilho|Fabrícia|F|', 'Dal-Pizzol|Felipe|F|']
D000818:Animals D001362:Avoidance Learning D001921:Brain D003072:Cognition Disorders D016207:Cytokines D006624:Hippocampus D007249:Inflammation D008297:Male D017628:Microglia D018384:Oxidative Stress D051381:Rats D017208:Rats, Wistar D018805:Sepsis D017392:Thiobarbituric Acid Reactive Substances
Microglia Encephalopathy Minocycline Sepsis Blood brain-barrier