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Phénomènes neuro-inflammatoires au cours de l'état de mal épileptique induit par le soman. Correction par des combinaisons atropine-kétamine.

Abstract : Epileptic seizures, status epilepticus (SE) and seizure-related brain damage (SRBD) due to organophosphorus nerve agent (OP) poisoning are accompanied by neuro-inflammatory events whose role in SRBD is not clear. Antagonists of the glutamatergic receptor NMDA, such as ketamine (KET), proved to be antiepileptic and neuroprotective even when SE is refractory to benzodiazepines 10 to 20 min after the initiation of seizures. Moreover, peripheral anti-inflammatory properties of KET have been described. To complement existing data, we studied the impact of soman poisoning on neuro-inflammatory response in murine cortex and hippocampus using different approaches (RT-qPCR, multiplex protein assays, histology). To assess the efficacy of KET on soman-induced neuro-inflammation 48 h after challenge, we determined the effects of two combinations of KET with atropine sulphate (KET/AS), administered either starting at 30 or 60 min post-challenge, on body weight loss, brain damage, and glial activation in the same brain areas. We also assessed their effects on inflammatory cytokines, chemokines and adhesion molecules (mRNA levels and protein content). After soman poisoning, we confirmed a massive microglial and astroglial activation and showed an increase of the mRNA and related protein levels for most of the inflammatory mediators studied. Both KET/AS treatment regimens proved highly neuroprotective but only partially suppressed glial activation. KET/AS also efficiently reduced the increase in mRNA and related pro-inflammatory markers provoked by the poisoning. As a conclusion, our results indicate that multiple inflammatory pathways are activated after soman poisoning. The present study also confirms that KET/AS treatment, even delayed up to one hour, is neuroprotective and limits the neuro-inflammatory response after soman intoxication.
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Contributor : Franck Dhote <>
Submitted on : Wednesday, January 26, 2011 - 11:40:12 AM
Last modification on : Wednesday, January 26, 2011 - 5:38:52 PM
Long-term archiving on: : Wednesday, April 27, 2011 - 2:52:46 AM


  • HAL Id : tel-00559682, version 1




Franck Dhote. Phénomènes neuro-inflammatoires au cours de l'état de mal épileptique induit par le soman. Correction par des combinaisons atropine-kétamine.. Neurosciences [q-bio.NC]. Université Joseph-Fourier - Grenoble I, 2010. Français. ⟨tel-00559682⟩



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