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Stanniocalcin 1 Inhibits the Inflammatory Response in Microglia and Protects Against Sepsis-Associated Encephalopathy
- Source :
- Neurotoxicity research. 39(2)
- Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Male
Inflammation
Pharmacology
Toxicology
medicine.disease_cause
Neuroprotection
Hippocampus
Sepsis
03 medical and health sciences
0302 clinical medicine
Medicine
Animals
Rats, Wistar
Neuroinflammation
Cells, Cultured
Glycoproteins
Microglia
business.industry
General Neuroscience
Sepsis-Associated Encephalopathy
medicine.disease
Disease Models, Animal
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
Mitochondrial respiratory chain
Neuroprotective Agents
Encephalitis
medicine.symptom
business
030217 neurology & neurosurgery
Oxidative stress
Subjects
Details
- ISSN :
- 14763524
- Volume :
- 39
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Neurotoxicity research
- Accession number :
- edsair.doi.dedup.....3fe4c72272dd17ceecf8600eccc3b098