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

Intensive Care Med. 2009 Apr;35(4):730-9. doi: 10.1007/s00134-009-1394-7. Epub 2009 Jan 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Chemokines / metabolism
  • DNA Primers / genetics
  • Delirium / etiology
  • Delirium / metabolism
  • Gene Expression / genetics*
  • Hippocampus / metabolism*
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxins / genetics*
  • Neurotoxins / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Norepinephrine / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Sepsis / complications
  • Sepsis / metabolism

Substances

  • Chemokines
  • DNA Primers
  • Neurotoxins
  • RNA, Messenger
  • Nitric Oxide Synthase
  • Norepinephrine