Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 190, Issue 1-2, Pages 101-111Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2007.08.014
Keywords
TLR4; cerebral; ischemia; repel-fusion
Categories
Funding
- NHLBI NIH HHS [R01 HL 071837, R01 HL071837, R01 HL071837-04, R01 HL071837-03, R01 HL071837-01A1, R01 HL071837-02] Funding Source: Medline
- NIGMS NIH HHS [GM 53552] Funding Source: Medline
Ask authors/readers for more resources
Toll-like receptors (TLRs) play a critical role in the induction of innate immune responses which have been implicated in neuronal death induced by global cerebral ischemia/reperfusion (GCI/R). The present study investigated the role and mechanisms-of-action of TLR4 signaling in ischemia-induced hippocampal neuronal death. Neuronal damage, activation of the TLR4 signaling pathway, expression of pro-inflammatory cytokines and activation of the PI3K/Akt signaling pathway in the hippocampal formation (HF) were assessed in wild type (WT) mice and TLR4 knockout (TLR4(-/-)) mice after GCI/R. GCI/R increased expression of TLR4 protein in the hippocampal formation (HF) and other brain structures in WT mice. Phosphorylation of the inhibitor of kappa B (p-I kappa B) as well as activation of nuclear factor kappa B (NF kappa B) increased in the HF of WT mice. In contrast, there were lower levels of p-I kappa B and NF kappa B binding activity in TLR4(-/-) mice subjected to GCI/R. Pro-inflammatory cytokine expression was also decreased, while phosphorylation of Akt and GSK3 beta were increased in the HF of TLR4(-/-) mice after GCI/R. These changes correlated with decreased neuronal death/apoptosis in TLR4(-/-) mice following GCI/R. These data suggest that activation of TLR4 signaling contributes to ischemia-induced hippocampal neuronal death. In addition, these data suggest that modulation of TLR4 signaling may attenuate ischemic injury in hippocampal neurons. (C) 2007 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available