Toll-like receptor 3 agonist Poly I:C protects against simulated cerebral ischemia in vitro and in vivo.

Abstract

AIM:

To examine the neuroprotective effects of the Toll-like receptor 3 (TLR3) agonist Poly I:C in acute ischemic models in vitro and in vivo.

METHODS:

Primary astrocyte cultures subjected to oxygen-glucose deprivation (OGD) were used as an in vitro simulated ischemic model. Poly I:C was administrated 2 h before OGD. Cell toxicity was measured using MTT assay and LDH leakage assay. The levels of TNFα, IL-6 and interferon-β (IFNβ) in the media were measured using ELISA. Toll/interleukin receptor domain-containing adaptor-inducing IFNβ (TRIF) protein levels were detected using Western blot analysis. A mouse middle cerebral artery occlusion (MCAO) model was u sed for in vivo study. The animals were administered Poly I:C (0.3 mg/kg, im) 2 h before MCAO, and examined with neurological deficit scoring and TTC staining. The levels of TNFα and IL-6 in ischemic brain were measured using ELISA.

RESULTS:

Pretreatment with Poly I:C (10 and 20 μg/mL) markedly attenuated OGD-induced astrocyte injury, and significantly raised the cell viability and reduced the LDH leakage. Poly I:C significantly upregulated TRIF expression accompanied by increased downstream IFNβ production. Moreover, Poly I:C significantly suppressed the pro-inflammatory cytokines TNFα and IL-6 production. In mice subjected to MCAO, administration of Poly I:C significantly attenuated the neurological deficits, reduced infarction volume, and suppressed the increased levels of TNFα and IL-6 in the ischemic striatum and cortex.

CONCLUSION:

Poly I:C pretreatment exerts neuroprotective and anti-inflammatory effects in the simulated cerebral ischemia models, and the neuroprotection is at least in part due to the activation of the TLR3-TRIF pathway.

• Authors: Lin-na Pan, Wei Zhu, Cai Li, Xu-lin Xu, Lian-jun Guo, Qing Lu
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 33 Issue 10 Pg. 1246-53 (Oct 2012) ISSN: 1745-7254 [Electronic] United States
• PMID: 22983393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media
• Neuroprotective Agents
• Toll-Like Receptor 3
• Glucose
• Poly I-C
• Oxygen

Topics

• Animals
• Astrocytes (drug effects, metabolism)
• Blotting, Western
• Cell Culture Techniques
• Cell Survival (drug effects)
• Cells, Cultured
• Culture Media
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Glucose (metabolism)
• Ischemic Attack, Transient (metabolism, prevention & control)
• Mice
• Neuroprotective Agents (pharmacology, therapeutic use)
• Oxygen (metabolism)
• Poly I-C (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Toll-Like Receptor 3 (agonists)