Literature DB >> 19156399

Endotoxin-induced gene expression differences in the brain and effects of iNOS inhibition and norepinephrine.

Stephanie Wolff1, Sabine Klatt, Jens C Wolff, Jochen Wilhelm, Ludger Fink, Manfred Kaps, Bernhard Rosengarten.   

Abstract

PURPOSE: We studied gene expression differences in brain homogenate, hippocampus, somatosensory cortex and cerebellum of rats suffering from sepsis-associated delirium and analyzed the effects of norepinephrine and 1,400 W (specific inhibitor of the inducible nitric-oxide synthase).
METHODS: We applied microarray screenings to rat brain homogenate 1, 3 and 4.5 h after lipopolysaccharide (LPS, 5 mg/kg) or 0.9% NaCl treatment. Therapy groups were analyzed after 4.5 h. Validations and compartment specific investigations were carried out by real-time PCR.
RESULTS: Most striking gene expression differences were seen 4.5 h after LPS administration, especially within the hippocampus (chemokines and endothelial cell-specific molecule 1). Norepinephrine resulted in a discrete chemokine up-regulation, while 1,400 W had hardly any effect.
CONCLUSION: Strongest gene regulations were found within the hippocampus. Norepinephrine showed a tendency of having a proinflammatory influence, while 1,400 W had no clear-cut effect onto the gene expression level.

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Year:  2009        PMID: 19156399     DOI: 10.1007/s00134-009-1394-7

Source DB:  PubMed          Journal:  Intensive Care Med        ISSN: 0342-4642            Impact factor:   17.440


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