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Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitation.

Publication ,  Journal Article
Cai, B; Chen, F; Ji, Y; Kiss, L; de Jonge, WJ; Conejero-Goldberg, C; Szabo, C; Deitch, EA; Ulloa, L
Published in: Journal of cellular and molecular medicine
September 2009

Severe haemorrhage is a common cause of death despite the recent advances in critical care. Conventional resuscitation fluids are designed to re-establish tissue perfusion, but they fail to prevent inflammatory responses during resuscitation. Our previous studies indicated that the vagus nerve can modulate systemic inflammation via the alpha7 nicotinic acetylcholine receptor (alpha7nAchR). Here, we report that the alpha7nAChR-agonist, GTS, restrains systemic inflammation and improves survival during resuscitation. Resuscitation with GTS rescued all the animals from lethal haemorrhage in a concentration-dependent manner. Unlike conventional resuscitation fluids, GTS inhibited the production of characteristic inflammatory and cardiodepressant factors including tumour necrosis factor (TNF) and high mobility group B protein-1 (HMGB1). Resuscitation with GTS was particularly effective in restraining systemic TNF responses and inhibiting its production in the spleen. At the molecular level, GTS inhibited p65RelA but not RelB NF-kappaB during resuscitation. Unlike non-specific nicotinic agonists, GTS inhibited serum protein TNF levels in both normal and splenectomized, haemorrhagic animals. Resuscitation with GTS inhibited poly(ADP-ribose) polymerase and systemic HMGB1 levels. Our studies suggest that GTS provides significant advantages as compared with non-specific nicotinic agonists, and it could be a promising anti-inflammatory supplement to improve survival during resuscitation.

Published In

Journal of cellular and molecular medicine

DOI

EISSN

1582-4934

ISSN

1582-1838

Publication Date

September 2009

Volume

13

Issue

9B

Start / End Page

3774 / 3785

Related Subject Headings

  • alpha7 Nicotinic Acetylcholine Receptor
  • Tumor Necrosis Factor-alpha
  • Treatment Outcome
  • Spleen
  • Resuscitation
  • Receptors, Nicotinic
  • Rats, Sprague-Dawley
  • Rats
  • Pyridines
  • Poly(ADP-ribose) Polymerases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Cai, B., Chen, F., Ji, Y., Kiss, L., de Jonge, W. J., Conejero-Goldberg, C., … Ulloa, L. (2009). Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitation. Journal of Cellular and Molecular Medicine, 13(9B), 3774–3785. https://doi.org/10.1111/j.1582-4934.2008.00550.x
Cai, Bolin, Fei Chen, Yan Ji, Levente Kiss, Wouter J. de Jonge, Concepcion Conejero-Goldberg, Csaba Szabo, Edwin A. Deitch, and Luis Ulloa. “Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitation.Journal of Cellular and Molecular Medicine 13, no. 9B (September 2009): 3774–85. https://doi.org/10.1111/j.1582-4934.2008.00550.x.
Cai B, Chen F, Ji Y, Kiss L, de Jonge WJ, Conejero-Goldberg C, et al. Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitation. Journal of cellular and molecular medicine. 2009 Sep;13(9B):3774–85.
Cai, Bolin, et al. “Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitation.Journal of Cellular and Molecular Medicine, vol. 13, no. 9B, Sept. 2009, pp. 3774–85. Epmc, doi:10.1111/j.1582-4934.2008.00550.x.
Cai B, Chen F, Ji Y, Kiss L, de Jonge WJ, Conejero-Goldberg C, Szabo C, Deitch EA, Ulloa L. Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitation. Journal of cellular and molecular medicine. 2009 Sep;13(9B):3774–3785.
Journal cover image

Published In

Journal of cellular and molecular medicine

DOI

EISSN

1582-4934

ISSN

1582-1838

Publication Date

September 2009

Volume

13

Issue

9B

Start / End Page

3774 / 3785

Related Subject Headings

  • alpha7 Nicotinic Acetylcholine Receptor
  • Tumor Necrosis Factor-alpha
  • Treatment Outcome
  • Spleen
  • Resuscitation
  • Receptors, Nicotinic
  • Rats, Sprague-Dawley
  • Rats
  • Pyridines
  • Poly(ADP-ribose) Polymerases