Neuroimmune Effects of Inhaling Low Dose Sarin
Abstract
The nerve gas sarin is a potent irreversible inhibitor of acetylcholine esterase that in high doses causes neurotoxicity seizures lung inflammation and death primarily from respiratory failure. Even in subclinical doses sarin suppresses the immune system and decreases serum corticosterone (CORT) levels. However the mechanism and duration these effects are not known. Our results that sarin upregulates the mRNA expression of proinflammatory cytokines in the lung which is associated with the activation of MAP kinases (ERK1/2) and the transcription factor NFkB. Sarin induced suppression of serum CORT level appear to be through its effects on the HPA axis. In addition higher doses of sarin that causes respiratory failure in animals result primarily from functional loss of central respiratory chemoreceptors. Moreover higher doses of sarin specifically damage the hippocampus and some regions of the cortex and might explain the long-term neurobehavioral problems seen in the survivors of Japanese sarin terrorism. Taken together these results suggest that will allow doses of sarin affect adaptive and innate immune responses and depress CORT and ACTH levels higher doses of sarin may cause death through loss of central respiratory chemoreceptors. Our preliminary results also suggest that exposure to high-doses of sarin (~LD50) may impair cognitive functions through injury to hippocampal and cortical neurons.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2008
- Accession Number
- ADA489047
Entities
People
- Mohan L. Sopori
Organizations
- Lovelace Foundation