Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil.
Laboratory of Clinical and Experimental Pathophysiology, Graduate Program in Health Sciences, University of South of Santa Catarina, Tubarão, SC, Brazil.
Brain Behav Immun. 2015 Jan;43:54-9. doi: 10.1016/j.bbi.2014.07.002. Epub 2014 Jul 11.
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.
氧化应激和炎症很可能是脓毒症相关脑病（SAE）和长期认知障碍发展的主要步骤。迄今为止，尚不清楚脑炎症和氧化损伤是全身炎症的直接后果，还是这些事件是由脑固有细胞（如小胶质细胞）驱动的。因此，本研究旨在评估米诺环素对脓毒症大鼠行为和神经炎症参数的影响。雄性 Wistar 大鼠通过盲肠结扎和穿刺（CLP）诱发脓毒症。动物分为假手术组（Sham+control）、假手术加米诺环素组（sham+MIN）、CLP 组（CLP+control）和 CLP 加米诺环素组（CLP+MIN）（100μg/kg，作为单次脑室内（ICV）注射给药）。一些动物在手术后 24 小时处死，以评估血脑屏障的破坏、细胞因子水平、海马体中脂质（TBARS）和蛋白质的氧化损伤。一些动物在恢复 10 天后进行下台阶抑制回避和旷场任务。米诺环素治疗可防止脓毒症后海马体氧化损伤和炎症标志物的增加。这与长期认知表现的改善有关。总之，我们证明了通过 ICV 注射米诺环素抑制小胶质细胞能够减少脓毒症幸存者的急性脑氧化损伤和炎症以及长期认知障碍。
