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


CONCLUSIONS
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.
Wolff
Stephanie
S
Department of Neurology, Justus-Liebig-University Giessen, Am Steg 14, 35392, Giessen, Germany. Stephanie.Wolff@neuro.med.uni-giessen.de
Klatt
Sabine
S
Wolff
Jens C
JC
Wilhelm
Jochen
J
Fink
Ludger
L
Kaps
Manfred
M
Rosengarten
Bernhard
B
D000818:Animals; D015153:Blotting, Western; D018925:Chemokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D003693:Delirium / Q000209:etiology / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism; D009498:Neurotoxins / Q000235:genetics* / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications / Q000378:metabolism
D018925:Chemokines; D017931:DNA Primers; D009498:Neurotoxins; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D009638:Norepinephrine