Stanniocalcin 1 Inhibits the Inflammatory Response in Microglia and Protects Against Sepsis-Associated Encephalopathy

被引：26

作者：

Bonfante, Sandra ^{[1
]}

Joaquim, Larissa ^{[1
]}

Fileti, Maria Eduarda ^{[1
]}

Della Giustina, Amanda ^{[1
]}

de Souza Goldim, Mariana Pereira ^{[1
]}

Danielski, Lucineia Gainski ^{[1
]}

Cittadin, Evandro ^{[1
]}

De Carli, Raquel Jaconi ^{[1
]}

de Farias, Bianca Xavier ^{[1
]}

Engel, Nicole Alessandra ^{[1
]}

Rosa, Naiana ^{[1
]}

Fortunato, Jucelia Jeremias ^{[1
]}

Giridharan, Vijayasree ^{[2
]}

Scaini, Giselli ^{[2
]}

Rezin, Gislaine Tezza ^{[1
]}

Generoso, Jaqueline ^{[3
]}

de Bitencourt, Rafael Mariano ^{[1
]}

Terra, Silvia ^{[4
]}

Barichello, Tatiana ^{[2
,3
]}

Petronilho, Fabricia ^{[1
,5
]}

机构：

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

[2] Univ Texas Hlth Sci Ctr Houston UTHlth, McGovern Med Sch, Faillace Dept Psychiat & Behav Sci, Translat Psychiat Program, Houston, TX 77054 USA

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

[4] Univ Fed Rio Grande do Sul UFRGS, Grad Program Biochem, Porto Alegre, RS, Brazil

[5] Univ Sul Santa Catarina, Lab Neurobiol Proc Inflamatorios & Metabol NEUROI, Programa Posgrad Ciencias Saude, Tubarao, SC, Brazil

来源：

NEUROTOXICITY RESEARCH | 2021年 / 39卷 / 02期

关键词：

Sepsis; Stanniocalcin-1; Microglia; Brain; TERM COGNITIVE IMPAIRMENT; CECAL LIGATION; CREATINE-KINASE; MITOCHONDRIAL DYSFUNCTION; ACUTE NEUROINFLAMMATION; RESPIRATORY-CHAIN; OXIDATIVE STRESS; BRAIN; APOPTOSIS; PROLIFERATION;

D O I：

10.1007/s12640-020-00293-y

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Sepsis-associated encephalopathy is a serious consequence of sepsis, triggered by the host response against an infectious agent, that can lead to brain damage and cognitive impairment. Several mechanisms have been proposed in this bidirectional communication between the immune system and the brain after sepsis as neuroinflammation, oxidative stress, and mitochondrial dysfunction. Stanniocalcin-1 (STC-1), an endogen neuroprotective protein, acts as an anti-inflammatory and suppresses superoxide generation through induction of uncoupling proteins (UCPs) in the mitochondria. Here, we demonstrated a protective role of STC-1 on inflammatory responses in vitro, in activated microglia stimulated with LPS, and on neuroinflammation, oxidative stress, and mitochondrial function in the hippocampus of rats subjected to an animal model of sepsis by cecal ligation and puncture (CLP), as well the consequences on long-term memory. Recombinant human STC-1 (rhSTC1) suppressed the pro-inflammatory cytokine production in LPS-stimulated microglia without changing the UCP-2 expression. Besides, rhSTC1 injected into the cisterna magna decreased acute hippocampal inflammation and oxidative stress and increased the activity of complex I and II activity of mitochondrial respiratory chain and creatine kinase at 24 h after sepsis. rhSTC1 was effective in preventing long-term cognitive impairment after CLP. In conclusion, rhSTC1 confers significant neuroprotection by inhibiting the inflammatory response in microglia and protecting against sepsis-associated encephalopathy in rats.

引用

页码：119 / 132

页数：14

共 71 条

[1]

AEBI H, 1984, METHOD ENZYMOL, V105, P121

[2] Hippocampus: a future target for sepsis treatment! [J].