Lipopolysaccharide-induced ischemic tolerance is associated with increased levels of ceramide in brain and in plasma.

Abstract

Intravenous administration of lipopolysaccharide (LPS) (0.9 mg/kg) has been shown to induce ischemic tolerance in spontaneously hypertensive rats (SHR). TNF-alpha is believed to play a crucial role in preconditioning as its inhibition with TNF-alpha-binding protein abolished tolerance. Our recent studies (Liu et al., Am. J. Physiol. 278 C144, 2000) have demonstrated that ceramide, a downstream messenger in TNF-alpha signaling, is a mediator of hypoxia-induced tolerance in neuronal cells. To test the hypothesis that ceramide contributes to LPS-induced tolerance in vivo, SHR were injected intravenously with either LPS or saline and the levels of ceramide in brain and in plasma were determined by reversed phase HPLC. LPS injection resulted in a significant increase of ceramide in plasma with a maximum at 24 h (8.32+/-1.14 pmol/microl (LPS) vs. 2.65+/-0.62 pmol/microl (saline)). LPS also induced ceramide upregulation in brain cortex, which started between 6 and 12 h and remained elevated up to 48 h after LPS injection. Fluorescent NBD-C6 ceramide was able to cross blood-brain barrier and was found in brain vessels, perivascular cells and in brain parenchyma 30 min after intravenous injection. These findings demonstrate that LPS preconditioning leads to elevation of ceramide in brain and plasma and, in conjunction with previous work, suggests that ceramide plays a role in LPS-induced protection against brain ischemic injury in vivo.

• Authors: C Zimmermann, I Ginis, K Furuya, D Klimanis, C Ruetzler, M Spatz, J M Hallenbeck
• Journal: Brain research (Brain Res) Vol. 895 Issue 1-2 Pg. 59-65 (Mar 23 2001) ISSN: 0006-8993 [Print] Netherlands
• PMID: 11259760 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ceramides
• Fluorescent Dyes
• Interleukin-6
• Lipopolysaccharides
• Neuroprotective Agents
• Tumor Necrosis Factor-alpha
• N-(7-(4-nitrobenzo-2-oxa-1,3-diazole))-6-aminocaproyl sphingosine
• 4-Chloro-7-nitrobenzofurazan

Topics

• 4-Chloro-7-nitrobenzofurazan (analogs & derivatives, pharmacology)
• Animals
• Blood-Brain Barrier (drug effects, physiology)
• Body Temperature (drug effects, physiology)
• Body Weight (drug effects, physiology)
• Brain (blood supply, drug effects, physiopathology)
• Brain Ischemia (drug therapy, metabolism, physiopathology)
• Ceramides (blood, pharmacology)
• Cerebrovascular Circulation (drug effects, physiology)
• Disease Models, Animal
• Fluorescent Dyes (pharmacology)
• Interleukin-6 (blood)
• Ischemic Preconditioning
• Leukocytes (cytology, drug effects, metabolism)
• Lipopolysaccharides (pharmacology)
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Inbred SHR
• Signal Transduction (drug effects, physiology)
• Tumor Necrosis Factor-alpha (metabolism)