Alpha-lipoic acid attenuates acute neuroinflammation and long-term cognitive impairment after polymicrobial sepsis

被引：47

作者：

Della Giustina, Amanda ^{[1
]}

Goldim, Mariana Pereira ^{[1
]}

Danielski, Lucineia Gainski ^{[1
]}

Florentino, Drielly ^{[1
]}

Mathias, Khiany ^{[1
]}

Garbossa, Leandro ^{[1
]}

Oliveira Junior, Aloir Neri ^{[1
]}

Fileti, Maria Eduarda ^{[1
]}

Zarbato, Graciela Freitas ^{[1
]}

da Rosa, Naiana ^{[1
]}

Martins Laurentino, Ana Olivia ^{[1
]}

Fortunato, Jucelia Jeremias ^{[1
]}

Mina, Francielle ^{[5
]}

Bellettini-Santos, Tatiani ^{[2
,3
,4
,5
]}

Budni, Josiane ^{[5
]}

Barichello, Tatiana ^{[5
]}

Dal-Pizzol, Felipe ^{[6
]}

Petronilho, Fabricia ^{[1
]}

机构：

[1] Univ South Santa Catarina, Lab Neurobiol Inflammatory & Metab Proc, Grad Program Hlth Sci, Tubarao, SC, Brazil

[2] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Translat Psychiat Program, Dept Psychiat & Behav Sci, Houston, TX 77030 USA

[3] Univ Texas Hlth Sci Ctr Houston, Ctr Excellence Mood Disorders, Dept Psychiat & Behav Sci, Houston, TX 77030 USA

[4] Univ Texas Houston, Grad Sch Biomed Sci Houston, Neurosci Grad Program, Houston, TX USA

[5] Univ Southern Santa Catarina, Lab Neurosci, Grad Program Hlth Sci, Hlth Sci Unit, Criciuma, SC, Brazil

[6] Univ Southern Santa Catarina, Lab Expt Pathophysiol, Grad Program Hlth Sci, Hlth Sci Unit, Criciuma, SC, Brazil

来源：

NEUROCHEMISTRY INTERNATIONAL | 2017年 / 108卷

关键词：

Sepsis; Antioxidant; Behavior; Blood brain barrier; Oxidative stress; Neuroinflammation; NF-KAPPA-B; INDUCED OXIDATIVE STRESS; NITRIC-OXIDE PRODUCTION; CECAL LIGATION; NEUROTROPHIC FACTOR; RAT-BRAIN; SUPEROXIDE-DISMUTASE; NITROSATIVE STRESS; ALZHEIMERS-DISEASE; ENDOTOXIC-SHOCK;

D O I：

10.1016/j.neuint.2017.06.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Sepsis is a complication of an infection which imbalance the normal regulation of several organ systems, including the central nervous system (CNS). Evidence points towards inflammation and oxidative stress as major steps associated with brain dysfunction in sepsis. Thus, we investigated the alpha-lipoic acid (ALA) effect as an important antioxidant compound on brain dysfunction in rats. Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) or sham (control) and treated orally with ALA (200 mg/kg after CLP) or vehicle. Animals were divided into sham + saline, sham + ALA, CLP + saline and CLP + ALA groups. Twelve, 24 h and 10 days after surgery, the hippocampus, prefrontal cortex and cortex were obtained and assayed for levels of TNF-alpha and IL-1 beta, blood brain barrier (BBB) permeability, nitrite/nitrate concentration, myeloperoxidase (MPO) activity, thiobarbituric acid reactive species (TBARS) formation, protein carbonyls, superoxide dismutase (SOD) and catalase (CAT) activity and neurotrophins levels. Behavioral tasks were performed 10 days after surgery. ALA reduced BBB permeability and TNF-alpha levels in hippocampus in 24 h and IL-1 beta levels and MPO activity in hippocampus and prefrontal cortex in 24 h. ALA reduced nitrite/nitrate concentration and lipid peroxidation in 24 h in all structures and protein carbonylation in 12 and 24 h in hippocampus and cortex. CAT activity increased in the hippocampus and cortex in all times. ALA enhanced NGF levels in hippocampus and cortex and prevented cognitive impairment. Our data demonstrates that ALA reduces the consequences of polymicrobial sepsis in rats by decreasing inflammatory and oxidative stress parameters in the brain. (C) 2017 Published by Elsevier Ltd.

引用

页码：436 / 447

页数：12

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