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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; Tel: 404-727-7614; Fax: 404-727-2388; Email: fhua2@emory.edu


Research Funding:

This work was supported by AHA National Program SDG 0830481N to FH, Emory University URC Grant (2009-002) to FH, research funding from the Department of Pediatric Cardiovascular Surgery at the Children’s Hospital of Atlanta and NIH RO1 NS04851 to DS.


  • TLRs
  • TRIF
  • cerebral ischemia/reperfusion
  • mouse

The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice


Journal Title:

Biochemical and Biophysical Research Communications


Volume 390, Number 3


, Pages 678-683

Type of Work:

Article | Post-print: After Peer Review


TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of Interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF’ role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NFκB and IRF-3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 hours after cerebral I/R. NF-κB activity and phosphorylation of the inhibitor of kappa B (IκBα) increased in ischemic brains, but IRF3, inhibitor of κB kinase complex-ε (IKKε), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-κB activity or p-IκBα induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-κB signaling and brain injury after acute cerebral I/R.

Copyright information:

© 2009 Elsevier Inc. 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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