Existing literature suggests that infection-specific mechanisms may play a significant role in the onset and progression of dementia, as opposed to the broader phenomenon of systemic inflammation. In addition, 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors have been proposed as a potential therapeutic approach for sepsis, given their anti-inflammatory and antioxidant properties. We investigated the neuroprotective effect of an HMG-CoA reductase inhibitor (simvastatin) by analyzing neurodegenerative markers, mitochondrial respiration, and neuronal tracing in the prefrontal cortex (PFC) and thalamic nucleus reuniens (RE) of sepsis survivor animals. Adult Wistar rats were subjected to sepsis by cecal ligation and puncture or left non-manipulated. The animals were treated with simvastatin or vehicle for 4 days before and 10 days after surgery. The treatment preserved the non-associative memory (P < 0.05), recovered expression of Smad-3 in the hippocampus (P < 0.05), and prevented increased expression of calpain-1 (hippocampus: P < 0.0001; PFC: P < 0.05) and GSKβ (hippocampus: P < 0.0001; PFC: P < 0.0001) in the brain structures of the sepsis survivor animals. These animals also showed mitochondrial dysfunction and decreased axon terminals in the RE. Simvastatin seems to restore energy metabolism by improving the electron transfer system (ETS) values in the hippocampus (P < 0.01) and the oxidative phosphorylation/ETS (P/E) ratio in the PFC (P < 0.05), in addition to preventing the reduction of axon terminals in survivor animals. These results suggest a potential neuroprotective effect and the importance of considering HMG-CoA reductase inhibitors as a possible adjuvant therapy in sepsis.

中文翻译：

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减轻认知领域的神经炎症：探索 HMG-CoA 还原酶抑制剂的影响。


现有文献表明，感染特异性机制可能在痴呆的发生和进展中发挥重要作用，而不是更广泛的全身炎症现象。此外，鉴于 3-羟基-3-甲基戊二酰 （HMG）-辅酶 A （CoA） 还原酶抑制剂具有抗炎和抗氧化特性，已被提议作为脓毒症的潜在治疗方法。我们通过分析脓毒症幸存动物前额叶皮层 （PFC） 和丘脑核 （RE） 中的神经退行性标志物、线粒体呼吸和神经元示踪来研究 HMG-CoA 还原酶抑制剂 （辛伐他汀） 的神经保护作用。成年 Wistar 大鼠通过盲肠结扎和穿刺进行败血症或保持不操纵。动物在手术前 4 天和手术后 10 天用辛伐他汀或载体治疗。治疗保留了非联想记忆 （P < 0.05），恢复了海马 Smad-3 的表达 （P < 0.05），并防止了钙蛋白酶-1 的表达增加 （海马： P < 0.0001;PFC：P < 0.05）和 GSKβ（海马：P < 0.0001;PFC：P < 0.0001）在败血症幸存动物的大脑结构中。这些动物还在 RE 中表现出线粒体功能障碍和轴突末梢减少。辛伐他汀似乎通过改善海马体中的电子传递系统 （ETS） 值 （P < 0.01） 和 PFC 中的氧化磷酸化/ETS （P/E） 比率 （P < 0.05） 来恢复能量代谢，此外还可以防止幸存动物轴突末端的减少。这些结果表明具有潜在的神经保护作用，以及考虑将 HMG-CoA 还原酶抑制剂作为脓毒症可能辅助治疗的重要性。