Prolonged inflammatory gene response following soman-induced seizures in mice
Autor: | André Peinnequin, Franck Dhote, Frédéric Dorandeu, Annie Foquin, Pierre Carpentier, Guy Lallement, Claire Delacour, Valérie Baille |
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Přispěvatelé: | Département de toxicologie, Service de Santé des Armées, Département de Radiobiologie et Radiopathologie, Service de Santé des Armées-Ministère de la Défense, Sinniger, Valérie |
Rok vydání: | 2007 |
Předmět: |
MESH: Inflammation
Male Cerebellum MESH: Hippocampus Time Factors MESH: Chemical Warfare Agents Interleukin-1beta Soman Hippocampus Suppressor of Cytokine Signaling Proteins Toxicology Epileptogenesis chemistry.chemical_compound Mice 0302 clinical medicine MESH: Interleukin-1beta Cortex (anatomy) MESH: Reverse Transcriptase Polymerase Chain Reaction MESH: Soman MESH: Animals Chemical Warfare Agents Cerebral Cortex 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction MESH: Tumor Necrosis Factors MESH: Seizures Intercellular Adhesion Molecule-1 MESH: Suppressor of Cytokine Signaling Proteins MESH: Gene Expression Regulation [SDV.TOX] Life Sciences [q-bio]/Toxicology medicine.anatomical_structure Cerebral cortex [SDV.TOX]Life Sciences [q-bio]/Toxicology Tumor Necrosis Factors medicine.symptom medicine.medical_specialty Brain damage Status epilepticus Biology 03 medical and health sciences Seizures Internal medicine medicine Animals RNA Messenger MESH: Mice 030304 developmental biology MESH: RNA Messenger Inflammation MESH: Intercellular Adhesion Molecule-1 MESH: Time Factors MESH: Cerebellum MESH: Cerebral Cortex MESH: Male Endocrinology chemistry Gene Expression Regulation Suppressor of Cytokine Signaling 3 Protein Immunology 030217 neurology & neurosurgery |
Zdroj: | Toxicology Toxicology, Elsevier, 2007, 238 (2-3), pp.166-76. ⟨10.1016/j.tox.2007.05.032⟩ |
ISSN: | 0300-483X |
DOI: | 10.1016/j.tox.2007.05.032⟩ |
Popis: | International audience; Following exposure to the organophosphorus nerve agent soman, the development of long-lasting seizures and build-up of irreversible seizure-related brain damage (SRBD) still represent a therapeutic challenge. A neuro-inflammatory reaction takes place in the brain after poisoning but its characteristics and potential role in SRBD and post-status epilepticus epileptogenesis is not well understood. In the present study we have analyzed by quantitative RT-PCR the time course of changes in mRNA levels of IL-1beta, TNFalpha, IL-6, ICAM-1 and SOCS3 in hippocampus, whole cortex and cerebellum in a mouse model of severe seizures and neuropathy up to 7 days after poisoning. Mice received an injection of the oxime HI-6 (50mg/kg) 5 min prior to the administration of a convulsive dose of soman (172 microg/kg). An important and highly significant increase of the five mRNA levels was recorded in cortex and hippocampus. In the cortex, the activation was generally detected as early as 1h post-intoxication with a peak response recorded between 6 and 24h. In the hippocampus, the gene up-regulation was delayed to 6h post-soman and the peak response observed between 24 and 48 h. After peaking, the response declined (except for ICAM in the hippocampus) but remained elevated, some of them significantly, at day 7. Interestingly, in the cerebellum, some changes were also observed but were several fold smaller. In conclusion, the present study indicates a quick neuro-inflammatory gene response that does not subside over 7 days suggesting a potential role in the neurological consequences of soman-induced status epilepticus. |
Databáze: | OpenAIRE |
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