Published in:
Open Access
01-04-2009 | Experimental
Endotoxin-induced gene expression differences in the brain and effects of iNOS inhibition and norepinephrine
Authors:
Stephanie Wolff, Sabine Klatt, Jens C. Wolff, Jochen Wilhelm, Ludger Fink, Manfred Kaps, Bernhard Rosengarten
Published in:
Intensive Care Medicine
|
Issue 4/2009
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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.