Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion.

Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion. Research Abstract Details 

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Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion. Abstract Text:

Fang Hua,Jing Ma,Tuanzhu Ha,Yeling Xia,Jim Kelley,David L Williams,Race L Kao,I William Browder,John B Schweitzer,John H Kalbfleisch,Chuanfu Li,Fang Hua,Jing Ma,Tuanzhu Ha,Yeling Xia,Jim Kelley,David L Williams,Race L Kao,I William Browder,John B Schweitzer,John H Kalbfleisch,Chuanfu Li,

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.

Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion. Publishing Authors By Initials

F Hua,J Ma,T Ha,Y Xia,J Kelley,DL Williams,RL Kao,IW Browder,JB Schweitzer,JH Kalbfleisch,C Li,F Hua,J Ma,T Ha,Y Xia,J Kelley,DL Williams,RL Kao,IW Browder,JB Schweitzer,JH Kalbfleisch,C Li,

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Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of neuroimmunology

VOLUME: 190

Page Numbers: 101-11

Journal Abbreviation: J. Neuroimmunol.

ISSN: 0165-5728

DAY: 19

MONTH: 09

YEAR: 2007

Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion. Information

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LANGUAGE: eng

NlmUniqueID: 8109498

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Grant and Affiliation Information for Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion.

AFFILIATION: Department of Surgery, East Tennessee State University, Johnson City, TN 37614, USA.

Country: Netherlands

AGENCY: United States NHLBI

GRANT: R01 HL 071837

ACRONYM: HL

MEDLINETA: J Neuroimmunol

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