Dexibuprofen (S(+)-isomer ibuprofen) reduces microglial activation and impairments of spatial working memory induced by chronic lipopolysaccharide infusion.

Full Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) have been proposed as a therapeutics to reduce the risk of Alzheimer's disease (AD). The present study shows that the peripheral administration of dexibuprofen (S(+)-isomer ibuprofen), which causes less gastric damage and has better anti-inflammatory effects than ibuprofen, reduces the microglial activation in the cortex and hippocampus, and reduces the phosphorylation of extracellular signal-regulated kinases in the hippocampus, which has been induced by chronic infusion of lipopolysaccharide (LPS) into the fourth ventricle of Wistar rats. The effects of dexibuprofen on impairments of spatial working memory induced by LPS infusions were measured with a trial-unique matching-to-place task in a water maze which assessed memory for place information over varying delays. When performing the water maze task, the rats with the LPS infusions showed spatial working memory impairments relative to the rats with the artificial cerebrospinal fluid. Daily administrations of dexibuprofen reduced the spatial working memory impairment induced by the chronic LPS infusion. The results indicate that NSAID treatments using dexibuprofen significantly attenuate the processes that drive the pathology associated with AD and that this process may involve the suppression of microglial activation.

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Author information

Author/s: Jin, Da-Qing (DQ); Sung, Jin-Young (JY); Hwang, Yoo Kyeong (YK); Kwon, Kyoung Ja (KJ); Han, Seol-Heui (SH); Min, Sun Seek (SS); Han, Jung-Soo (JS);

Affiliation: Graduate Program in Neuroscience, Institute for Brain Science and Technology (IBST), Inje University, Daejeon, South Korea.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav), published in United States. (Language: eng)

Reference: 2008-May; vol 89 (issue 3) : pp 404-11

Dates: Created 2008/03/21; Completed 2008/05/20;

PMID: 18295322, status: MEDLINE (last retrieval date: 11/6/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Cerebral Cortex - drug effects; enzymology
Extracellular Signal-Regulated MAP Kinases - metabolism
Hippocampus - drug effects; enzymology
Indoprofen - pharmacology

Lipopolysaccharides - toxicity
Male
Memory, Short-Term - drug effects
Microglia - drug effects; physiology
Rats
Rats, Wistar

Associated Chemicals: Anti-Inflammatory Agents, Non-Steroidal (0) ; Lipopolysaccharides (0) ; Indoprofen (31842-01-0) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.1.37)

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