Studies on Neuronal Apoptosis Following Soman Exposure in the Rat
Abstract
Exposure to chemical warfare nerve agents (CWNA) is an ongoing threat to military personnel and civilian populations. The pathological consequences of CWNA exposure, including apoptosis, have not been well characterized. In the present study we have characterized the time course of the neuronal apoptotic events (caspase-3 activation, high molecular weight DNA fragmentation and Comet assay analysis) occurring out to 48 h following Soman exposure. Male Sprague-Dawley rats were pre-treated with the oxime HI-6 (125 mg/kg, i.p.) and exposed 30 min later to 1.6x LD50 of Soman (180 g/kg, s.c.) followed at 1 min by atropine (4 mg/kg, i.m.). Brains were removed and three brain regions (thalamus, hippocampus and piriform cortex) dissected at several post-exposure time points to evaluate parameters of apoptosis. A significant increase in caspase-3 activation was measured 2 h and 6 h post-exposure which was maximum at 2 h post-exposure. Highest activation of caspase-3 was observed in the thalamus followed by hippocampus and piriform cortex. Comet assay analysis showed significantly increased apoptosis and DNA fragmentation at 24 and 48 h post-exposure. Apoptosis was maximal in the thalamus at 24 h, followed by hippocampus and piriform cortex. In conclusion, an apoptotic cascade is activated following Soman exposure, which along with necrotic cell death may be involved in the neuropathology associated with Soman exposure.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2005
- Accession Number
- ADA448956
Entities
People
- F. C. Tortella
- I. Koplovitz
- J. R. Dave
- John R. Moffett
- L. C. Velarde
- M. J. Williams
- R. A. Price
- S. M. Schulz
Organizations
- United States Army Medical Research Institute of Chemical Defense