| Title | Changes in mouse brain metabolism following a convulsive dose of soman: a proton hrmas nmr study. | | Author(s) | Fauvelle F, Dorandeu F, Carpentier P, Foquin A, Rabeson H, Graveron-Demilly D, Arvers P, Testylier G | | Institution | Unité de Biophysique Cellulaire et Moleculaire, Institut de Recherche Biomédicale des Armées - Centre de Recherches du Service Santé des Armées, BP87, 38 702 La Tronche cedex, France. | | Source | Toxicology 2009 Oct 30. | | Abstract | Soman, an irreversible organophosphorus cholinesterase inhibitor, induces status epilepticus and, in sensitive brain areas, seizure-related brain damage (e.g., brain edema and neuronal loss). The brain metabolic disturbances associated with these events are ill known. In the present study, we thus evaluated these changes in a murine model of soman-induced status epilepticus up to 7 d after intoxication. Mice, protected by HI-6 and atropine methyl nitrate, were poisoned with soman (172mug/kg) and then sacrificed at set time points, from 1h to 7 d. Brain biopsies from the piriform cortex (Pir) and cerebellum (Cer) were analyzed by (1)H HRMAS NMR spectroscopy. Spectra were then analysed using both a supervised multivariate analysis and the QUEST procedure of jMRUI for the quantification of 17 metabolites. The multivariate analysis clearly showed the metabolic differences between a damaged structure (Pir) and a structure with less prominent changes (cerebellum) and helped to globally assess the time course of metabolic changes. Analysis of the individual metabolites showed that the major changes took place in the piriform cortex but that cerebellum was not change-free. The most prominent changes in the former were an early (1 - 4h) increase in alanine and acetate, a delayed increase in lactate, glycerophosphocholine and glutamine as well as a delayed decrease in myo-inositol and N-acetylaspartate. A week after poisoning, some metabolic disturbances were still present. Further research will be necessary to clarify what could be the involvement of these metabolites in physiological processes and how they might become useful surrogate markers of brain damage and repair. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19883723 |
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