PMID- 17884182
OWN - NLM
STAT- MEDLINE
DCOM- 20071221
LR  - 20181113
IS  - 0165-5728 (Print)
IS  - 0165-5728 (Linking)
VI  - 190
IP  - 1-2
DP  - 2007 Oct
TI  - Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal 
      death following global cerebral ischemia/reperfusion.
PG  - 101-11
AB  - 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-IkappaB) as well as activation of 
      nuclear factor kappa B (NFkappaB) increased in the HF of WT mice. In contrast, 
      there were lower levels of p-IkappaB and NFkappaB binding activity in TLR4(-/-) 
      mice subjected to GCI/R. Pro-inflammatory cytokine expression was also decreased, 
      while phosphorylation of Akt and GSK3beta 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.
FAU - Hua, Fang
AU  - Hua F
AD  - Department of Surgery, East Tennessee State University, Johnson City, TN 37614, 
      USA.
FAU - Ma, Jing
AU  - Ma J
FAU - Ha, Tuanzhu
AU  - Ha T
FAU - Xia, Yeling
AU  - Xia Y
FAU - Kelley, Jim
AU  - Kelley J
FAU - Williams, David L
AU  - Williams DL
FAU - Kao, Race L
AU  - Kao RL
FAU - Browder, I William
AU  - Browder IW
FAU - Schweitzer, John B
AU  - Schweitzer JB
FAU - Kalbfleisch, John H
AU  - Kalbfleisch JH
FAU - Li, Chuanfu
AU  - Li C
LA  - eng
GR  - R01 HL071837-01A1/HL/NHLBI NIH HHS/United States
GR  - R01 HL071837/HL/NHLBI NIH HHS/United States
GR  - R01 HL071837-02/HL/NHLBI NIH HHS/United States
GR  - R01 HL071837-03/HL/NHLBI NIH HHS/United States
GR  - GM 53552/GM/NIGMS NIH HHS/United States
GR  - R01 HL071837-04/HL/NHLBI NIH HHS/United States
GR  - R01 HL 071837/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070919
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Cytokines)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/*immunology/metabolism/physiopathology
MH  - Cell Death/drug effects/immunology
MH  - Cerebral Infarction/*immunology/metabolism/physiopathology
MH  - Cytokines/metabolism
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Hippocampus/*immunology/pathology/physiopathology
MH  - I-kappa B Proteins/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-kappa B/metabolism
MH  - Nerve Degeneration/*immunology/pathology/physiopathology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Reperfusion Injury/*immunology/metabolism/physiopathology
MH  - Signal Transduction/genetics/immunology
MH  - Toll-Like Receptor 4/genetics/*immunology
MH  - Up-Regulation/genetics/immunology
PMC - PMC2453597
MID - NIHMS34119
EDAT- 2007/09/22 09:00
MHDA- 2007/12/22 09:00
PMCR- 2008/10/01
CRDT- 2007/09/22 09:00
PHST- 2007/06/15 00:00 [received]
PHST- 2007/08/06 00:00 [revised]
PHST- 2007/08/27 00:00 [accepted]
PHST- 2007/09/22 09:00 [pubmed]
PHST- 2007/12/22 09:00 [medline]
PHST- 2007/09/22 09:00 [entrez]
PHST- 2008/10/01 00:00 [pmc-release]
AID - S0165-5728(07)00301-3 [pii]
AID - 10.1016/j.jneuroim.2007.08.014 [doi]
PST - ppublish
SO  - J Neuroimmunol. 2007 Oct;190(1-2):101-11. doi: 10.1016/j.jneuroim.2007.08.014. 
      Epub 2007 Sep 19.