A common consequence of exposure to
organophosphate nerve agents is the centrally mediated seizure activity that appears even after conventional treatment with
atropine and
oximes. We have previously demonstrated a major inflammatory response with subsequent brain damage which was correlated with the duration of the
sarin-induced
seizures (Chapman et al., 2006). In the present work
seizures were induced by the
nerve agent sarin (1.2 LD50) insufficiently treated 1 min later by
atropine and
trimedoxime bromide (TA), with additional
midazolam treatment either 5 or 30 min after continuous seizure activity. The efficacy of both steroidal and nonsteroidal anti-inflammatory drugs (
NSAIDs), as well as other drugs that were reported as beneficial in neuroprotection, were evaluated for their contribution as adjunct treatment against
sarin induced
seizures and the ensuing inflammatory brain damage. Results show that both
steroids and
NSAIDs were harmful when administered during convulsions, and
steroids were at best ineffective if administered at their termination. However, if administered at termination of convulsions, the
NSAID ibuprofen, the selective
COX 2 inhibitor nimesulide and the PLA2 inhibitor
quinacrine were partially effective in reducing brain inflammatory markers. Administration of exogenous analogs of
prostaglandins (
PGE2) immediately following
sarin-induced convulsions was found to have a beneficial effect in reducing brain inflammatory markers measured at 24 h and one week post
sarin exposure. These findings support the hypothesis that elevated levels of PGE2 have a beneficial role immediately following
sarin induced
seizures, and that early inhibition of
PGE2 production by both
steroids and
NSAID is contraindicative.