Laboratory of Neurosciences, National Institute for Translational Medicine (INCT-TM), Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000, Criciúma, Santa Catarina, Brazil; Laboratory of Experimental Pathophysiology, National Institute for Translational Medicine (INCT-TM), Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000, Criciúma, Santa Catarina, Brazil.
Synapse. 2013 Nov;67(11):786-93. doi: 10.1002/syn.21686. Epub 2013 Jul 4.
Central nervous system (CNS) dysfunction secondary to sepsis is characterized by long-term cognitive impairment. It was observed that oxidative damage, energetic metabolism impairment, and cytokine level alteration seen in early times in an animal model of sepsis may persist for up to 10 days and might be associated with cognitive damage. In order to understand these mechanisms, at least in part, we evaluated the effects of sepsis on cytokine levels in the cerebrospinal fluid (CSF), oxidative parameters, and energetic metabolism in the brain of rats at both 30 and 60 days after sepsis induction by cecal ligation and perforation (CLP). To this aim, male Wistar rats underwent CLP with "basic support" or were sham-operated. Both 30 and 60 days after surgery, the CSF was collected and the animals were killed by decapitation. Then, the prefrontal cortex, hippocampus, striatum, and cortex were collected. Thirty days after surgery, an increase of IL-6 level in the CSF; an increase in the thiobarbituric acid-reactive species (TBARS) in prefrontal cortex and a decrease in hippocampus, striatum, and cortex; a decrease of carbonyl protein formation only in prefrontal cortex and an increase in striatum; and an increase in the complex IV activity only in hippocampus were observed. Sixty days after sepsis, an increase of TNF-α level in the CSF; a decrease of TBARS only in hippocampus; an increase of carbonyl protein formation in striatum; and a decrease of complex I activity in prefrontal cortex, hippocampus, and striatum were observed. These findings may contribute to understanding the role of late cognitive impairment. Further studies may address how these findings interact during sepsis development and contribute to CNS dysfunction.
中枢神经系统（CNS）功能障碍继发于脓毒症，其特征是长期认知障碍。有人观察到，在脓毒症动物模型中早期出现的氧化损伤、能量代谢障碍和细胞因子水平改变可能持续长达 10 天，并且可能与认知损伤有关。为了至少部分理解这些机制，我们评估了脓毒症对大脑中脑脊液（CSF）、氧化参数和能量代谢中细胞因子水平的影响，这些影响在通过盲肠结扎穿孔（CLP）诱导脓毒症后 30 天和 60 天的大鼠中观察到。为此，雄性 Wistar 大鼠接受 CLP 并给予“基本支持”或假手术。手术后 30 天和 60 天，收集 CSF 并通过断头处死动物。然后，采集前额叶皮质、海马体、纹状体和皮质。手术后 30 天，CSF 中 IL-6 水平升高；前额叶皮质中丙二醛反应性物质（TBARS）增加，而海马体、纹状体和皮质中减少；仅在前额叶皮质中羰基蛋白形成减少，而在纹状体中增加；仅在海马体中复合物 IV 活性增加。脓毒症后 60 天，CSF 中 TNF-α水平升高；仅在海马体中 TBARS 减少；纹状体中羰基蛋白形成增加；而在前额叶皮质、海马体和纹状体中复合物 I 活性减少。这些发现可能有助于理解迟发性认知障碍的作用。进一步的研究可能会研究这些发现如何在脓毒症发展过程中相互作用，并对中枢神经系统功能障碍做出贡献。
