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

Fang Hua, Jun Wang, Iqbal Sayeed, Tauheed Ishrat, Fahim Atif, Donald G. Stein

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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's 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 NF-κB and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h 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.

Original languageEnglish (US)
Pages (from-to)678-683
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume390
Issue number3
DOIs
StatePublished - Dec 18 2009
Externally publishedYes

Fingerprint

NF-kappa B
Reperfusion Injury
Brain Ischemia
Interferon Regulatory Factor-3
Brain
Chemical activation
Reperfusion
Brain Infarction
Phosphorylation
R Factors
Toll-Like Receptors
Middle Cerebral Artery Infarction
Pathologic Processes
Knockout Mice
Brain Injuries
Proteins
Phosphotransferases
Ischemia
Western Blotting
Enzyme-Linked Immunosorbent Assay

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice. / Hua, Fang; Wang, Jun; Sayeed, Iqbal; Ishrat, Tauheed; Atif, Fahim; Stein, Donald G.

In: Biochemical and Biophysical Research Communications, Vol. 390, No. 3, 18.12.2009, p. 678-683.

Research output: Contribution to journalArticle

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