TY - JOUR
T1 - Stanniocalcin 1 Inhibits the Inflammatory Response in Microglia and Protects Against Sepsis-Associated Encephalopathy
AU - Bonfante, Sandra
AU - Joaquim, Larissa
AU - Fileti, Maria Eduarda
AU - Giustina, Amanda Della
AU - de Souza Goldim, Mariana Pereira
AU - Danielski, Lucinéia Gainski
AU - Cittadin, Evandro
AU - De Carli, Raquel Jaconi
AU - de Farias, Bianca Xavier
AU - Engel, Nicole Alessandra
AU - da Rosa, Naiana
AU - Fortunato, Jucélia Jeremias
AU - Giridharan, Vijayasree
AU - Scaini, Giselli
AU - Rezin, Gislaine Tezza
AU - Generoso, Jaqueline
AU - de Bitencourt, Rafael Mariano
AU - Terra, Silvia
AU - Barichello, Tatiana
AU - Petronilho, Fabricia
N1 - Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - Brain
KW - Microglia
KW - Sepsis
KW - Stanniocalcin-1
UR - http://www.scopus.com/inward/record.url?scp=85092161682&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092161682&partnerID=8YFLogxK
U2 - 10.1007/s12640-020-00293-y
DO - 10.1007/s12640-020-00293-y
M3 - Article
C2 - 33025358
AN - SCOPUS:85092161682
SN - 1029-8428
VL - 39
SP - 119
EP - 132
JO - Neurotoxicity Research
JF - Neurotoxicity Research
IS - 2
ER -