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Updated: Jul 14, 2026
A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia
Published on: August 18, 2015
TLR2 has a detrimental role in mouse transient focal cerebral ischemia
Gina Ziegler1, Denise Harhausen, Claudia Schepers
1Max-Planck-Institute for Molecular Genetics, Ihnestr. 73, 14195 Berlin, Germany.
Abstract:
A significant up-regulation of Toll-like-receptor (TLR) mRNAs between 3 and 48 h reperfusion time after induction of transient focal cerebral ischemia for 1h was revealed by applying global gene expression profiling in postischemic mouse brains. Compared to TLR4 and TLR9, TLR2 proved to be the most significantly up-regulated TLR in the ipsilateral brain hemisphere. TLR2-protein was found to be expressed mainly in microglia in the postischemic brain tissue, but also in selected endothelial cells, neurons, and astrocytes. Additionally, TLR2-related genes with pro-inflammatory and pro-apoptotic capabilities were induced. Therefore we hypothesized that TLR2-signaling could exacerbate the primary brain damage after ischemia. Two days after induction of transient focal cerebral ischemia (1h), we found a significant decrease of the infarct volume in TLR2 deficient mice compared to wild type mice (75+/-5 vs. 42+/-7 mm(3)). We conclude that TLR2 up-regulation and TLR2-signaling are important events in focal cerebral ischemia and contribute to the deterioration of ischemic damage.
Insights
Toll-like receptor 2 (TLR2) is upregulated after stroke, exacerbating brain damage. TLR2 deficiency significantly reduces stroke injury, highlighting TLR2 as a therapeutic target for ischemic stroke.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Transient focal cerebral ischemia induces significant changes in gene expression in the brain.
- Toll-like receptors (TLRs) play crucial roles in immune responses and inflammation.
- Previous studies have implicated TLRs in various neurological conditions.
Purpose of the Study:
- To investigate the role of Toll-like receptor 2 (TLR2) in the response to transient focal cerebral ischemia.
- To determine if TLR2 signaling exacerbates brain damage following ischemic events.
- To evaluate the therapeutic potential of targeting TLR2 in ischemic stroke.
Main Methods:
- Global gene expression profiling was used to identify upregulated TLRs in postischemic mouse brains.
- Immunohistochemistry was employed to determine the cellular localization of TLR2 protein.
- Infarct volumes were measured in TLR2-deficient and wild-type mice after inducing transient focal cerebral ischemia.
Main Results:
- Toll-like receptor 2 (TLR2) mRNA was significantly upregulated between 3 and 48 hours post-ischemia.
- TLR2 protein expression was primarily observed in microglia, with additional presence in endothelial cells, neurons, and astrocytes.
- TLR2-deficient mice exhibited a significant reduction in infarct volume compared to wild-type controls.
- Pro-inflammatory and pro-apoptotic genes related to TLR2 signaling were induced post-ischemia.
Conclusions:
- TLR2 upregulation and signaling are critical events in the pathophysiology of focal cerebral ischemia.
- TLR2 contributes to the exacerbation of ischemic brain damage.
- Targeting TLR2 signaling presents a potential therapeutic strategy for mitigating stroke-induced injury.
