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Author Notes:

Correspondence: Fang Hua, MD., PhD., Department of Emergency Medicine, Brain Research Laboratory, Emory University, 1365B Clifton Road, Suite 5100, Atlanta, GA 30322; Phone: 404-727-7614; Fax: 404-727-2388; Email: fhua2@emory.edu

Acknowledgments: The authors wish to thank Dr. Donald G. Stein for his critical reading of the manuscript.

Subjects:

Research Funding:

This work was supported by AHA postdoctoral fellowship 0625348B and AHA Scientist Development Grant 0830481N to FH; ETSU RDC Grant to RLK; NIH RO1GM53552 to DLW and NIH RO1HL071837 to CL.

Keywords:

  • TLR2
  • TLR4
  • cerebral
  • ischemia/reperfusion
  • mouse

Differential roles of TLR2 and TLR4 in acute focal cerebral ischemia/reperfusion injury in mice

Tools:

Journal Title:

Brain Research

Volume:

Volume 1262

Publisher:

, Pages 100-108

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Recent studies have shown that Toll-like receptors (TLRs) are involved in cerebral ischemia/reperfusion (I/R) injury. This study was to investigate the role of TLR2 and TLR4 in acute focal cerebral I/R injury. Cerebral infarct size, neurological function and mortality were evaluated. NFκB binding activity, phosphorylation of IκBα, Akt and ERK1/2 were examined in ischemic cerebral tissue by EMSA and Western blots. Compared to wild type (WT) mice, in TLR4 knockout (TLR4KO) mice, brain infarct size was decreased (2.6 ± 1.18% vs 11.6 ± 1.97% of whole cerebral volume, p<0.05) and neurological function was maintained (7.3 ± 0.79 vs 4.7 ± 0.68, p<0.05). However, compared to TLR4KO mice, TLR2 knockout (TLR2KO) mice showed higher mortality (38.2% vs 13.0%, p<0.05), decreased neurological function (2.9 ± 0.53 vs 7.3 ± 0.79, p<0.05) and increased brain infarct size (19.1 ± 1.33% vs 2.6 ± 1.18%, p<0.05). NFκB activation and IκBα phosphorylation were attenuated in TLR4KO mice (1.09 ± 0.02 and 1.2 ± 0.04) compared to TLR2KO mice (1.31 ± 0.02 and 2.2 ± 0.32) after cerebral ischemia. Compared to TLR4KO mice, in TLR2KO mice, the phosphorylation of Akt (0.2 ± 0.03 vs 0.9 ± 0.16, p<0.05) and ERK1/2 (0.8 ± 0.06 vs 1.3 ± 0.17) evoked by cerebral I/R was attenuated. The present study demonstrates that TLR2 and TLR4 play differential roles in acute cerebral I/R injury. Specifically, TLR4 contributes to cerebral I/R injury, while TLR2 appears to be neuroprotective by enhancing the activation of protective signaling in response to cerebral I/R.

Copyright information:

© 2009 Elsevier B.V. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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