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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2012

Open Access 01-12-2012 | Research

Toll-like receptor 2 deficiency leads to delayed exacerbation of ischemic injury

Authors: Ivan Bohacek, Pierre Cordeau, Mélanie Lalancette–Hébert, Dunja Gorup, Yuan-Cheng Weng, Srecko Gajovic, Jasna Kriz

Published in: Journal of Neuroinflammation | Issue 1/2012

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Abstract

Background

Using a live imaging approach, we have previously shown that microglia activation after stroke is characterized by marked and long-term induction of the Toll-like receptor (TLR) 2 biophotonic signals. However, the role of TLR2 (and potentially other TLRs) beyond the acute innate immune response and as early neuroprotection against ischemic injury is not well understood.

Methods

TLR2−/− mice were subjected to transient middle cerebral artery occlusion followed by different reperfusion times. Analyses assessing microglial activation profile/innate immune response were performed using in situ hybridization, immunohistochemistry analysis, flow cytometry and inflammatory cytokine array. The effects of the TLR2 deficiency on the evolution of ischemic brain injury were analyzed using a cresyl violet staining of brain sections with appropriate lesion size estimation.

Results

Here we report that TLR2 deficiency markedly affects post-stroke immune response resulting in delayed exacerbation of the ischemic injury. The temporal analysis of the microglia/macrophage activation profiles in TLR2−/− mice and age-matched controls revealed reduced microglia/macrophage activation after stroke, reduced capacity of resident microglia to proliferate as well as decreased levels of monocyte chemotactic protein-1 (MCP-1) and consequently lower levels of CD45high/CD11b+ expressing cells as shown by flow cytometry analysis. Importantly, although acute ischemic lesions (24 to 72 h) were smaller in TLR2−/− mice, the observed alterations in innate immune response were more pronounced at later time points (at day 7) after initial stroke, which finally resulted in delayed exacerbation of ischemic lesion leading to larger chronic infarctions as compared with wild-type mice. Moreover, our results revealed that TLR2 deficiency is associated with significant decrease in the levels of neurotrophic/anti-apoptotic factor Insulin-like growth factor-1 (IGF-1), expressed by microglia in the areas both in and around ischemic lesion.

Conclusion

Our results clearly suggest that optimal and timely microglial activation/innate immune response is needed to limit neuronal damage after stroke.
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Metadata
Title
Toll-like receptor 2 deficiency leads to delayed exacerbation of ischemic injury
Authors
Ivan Bohacek
Pierre Cordeau
Mélanie Lalancette–Hébert
Dunja Gorup
Yuan-Cheng Weng
Srecko Gajovic
Jasna Kriz
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-9-191

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