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Journal of Neuroinflammation

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Open Access 01-12-2013 | Research

TLR-3 receptor activation protects the very immature brain from ischemic injury

Authors: Hui Shi, Nadia Gabarin, Edward Hickey, Rand Askalan

Published in: Journal of Neuroinflammation | Issue 1/2013

Abstract

Background

We have shown that preconditioning by lipopolysaccharide (LPS) will result in 90% reduction in ischemic brain damage in P7 rats. This robust LPS neuroprotection was not observed in P3 or P5 pups (corresponding to human premature infant). LPS is a known Toll-like receptor 4 (TLR-4) ligand. We hypothesized that TLRs other than TLR-4 may mediate preconditioning against cerebral ischemic injury in the developing brain.

Methods

TLR-2, TLR-3, TLR-4, and TLR-9 expression was detected in brain sections from P3, P5, and P7 rats by immuno-staining. In subsequent experiments, P5 rats were randomly assigned to TLR-3 specific agonist, poly I:C, or saline treated group. At 48 h after the injections, hypoxic-ischemic (HI) injury was induced by unilateral carotid artery ligation followed by hypoxia for 65 min. Brains were removed 1 week after HI injury and infarct volumes were compared in H&E stained sections between the two groups.

Results

TLR-2 and TLR-3 were highly expressed in brains of P3 and P5 but not in P7 rats. The number of TLR-4 positive cells was lower in P3 and P5 compared to P7 brains (P <0.05). TLR-3 was predominately expressed in P5 pups (P <0.05). There was no significant difference in TLR-9 expression in the three age groups. There was a significant reduction in infarct volume (P = 0.01) in poly I:C compared to saline pre-treated P5 pups. Pre-treatment with poly I:C downregulated NF-κB and upregulated IRF3 expression in P5 rat ischemic brains. Pre-treatment with poly I:C did not offer neuroprotection in P7 rat brains.

Conclusion

TLRs expression and function is developmentally determined. Poly I:C-induced preconditioning against ischemic injury may be mediated by modulation of TLR-3 signaling pathways. This is the first study to show that TLR-3 is expressed in the immature brain and mediates preconditioning against ischemic injury.

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Title: TLR-3 receptor activation protects the very immature brain from ischemic injury
Authors: Hui Shi
Nadia Gabarin
Edward Hickey
Rand Askalan
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2013
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-10-104

Keynote webinar | Spotlight on medication adherence

Springer Medicine

TLR-3 receptor activation protects the very immature brain from ischemic injury

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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