Time dependent dual effect of anti-inflammatory treatments on sarin-induced brain inflammation: suggested role of prostaglandins.

08:00 EDT 13th May 2019 | BioPortfolio

Summary of "Time dependent dual effect of anti-inflammatory treatments on sarin-induced brain inflammation: suggested role of prostaglandins."

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.


Journal Details

This article was published in the following journal.

Name: Neurotoxicology
ISSN: 1872-9711


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Medical and Biotech [MESH] Definitions

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Substances that display the physical properties of ELASTICITY and VISCOSITY. The dual-nature of these substances causes them to resist applied forces in a time-dependent manner.

A non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase.

An anti-inflammatory, synthetic glucocorticoid. It is used topically as an anti-inflammatory agent and in aerosol form for the treatment of ASTHMA.

A non-steroidal anti-inflammatory agent (ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL) similar in mode of action to INDOMETHACIN.

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