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
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