Central Nervous System Controls Pulmonary Inflammation during Septic Shock

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Issue Date
2014
Authors
Peng, Jianya '14
Degree
MS in Pharmaceutical Sciences
Advisor
Feleder, Carlos
Committee Members
Johnson, Arnold
Malik, Meenakshi
Journal Title
Journal ISSN
Volume Title
Abstract
To investigate the participation of the central endocannabinoid in mediating acute lung inflammation (ALI) during septic shock, the hypothesis was tested that the brain endocannabinoid type 1 (CB-1) receptor antagonist rimonabant prevents lipopolysaccharide (LPS) induced lung inflammation. Rats were pretreated with rimonabant (500ng) or vehicle by an intracerebroventricular (ICV) injection 5 minutes prior to intravenous (IV) injection of either LPS (5 mg/kg) or saline, followed by additional ICV injections at 1.5 and 3 hours post-LPS in the 4 hour treatment groups. Lungs were removed at 30 minutes or 4 hours after IV injection. The isolated-perfused lung was assessed for hemodynamics. Lung homogenates were assessed for Toll-like receptor 4 (TLR4) signaling cascade markers and α7 nicotinic acetylcholine receptor (α7nAChR) activity.
Conclusions: The data indicate that antagonism of the central CB-1 receptors inhibits the initiation and progression of the lung inflammatory response to LPS.
Citation
Peng J. Central nervous system controls pulmonary inflammation during septic shock [thesis]. Ann Arbor (MI): Proquest/UMI; 2014. 84 p.
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