title: Central neuro-inflammatory gene response following soman exposure in the rat.
abstract: Effective treatments to improve survivability following exposure to the nerve agent soman have been established and are currently available. Unfortunately, electrographic brain seizures, neuroinflammation and brain cell death are still a potential problem even with treatment. In the present study we have characterized the time course of the central neuro-inflammatory gene response using quantitative real time-PCR (TaqMan). Male Sprague-Dawley rats were pre-treated with HI-6 (1-2-hydroxy-iminomethyl-1-pyridino-3-(4-carbamoyl-1-pyridino-2-oxapropane dichloride); 125 mg/kg, i.p.) and exposed 30 min later to 1.6 x LD(50) of soman (pinacolyl methyl-phosphonofluoridate, 180 microg/kg, s.c.) followed at 1 min by atropine methyl nitrate (4 mg/kg, i.m.). Initially, a significant and dramatic upregulation of tumor necrosis factor-alpha and vascular cell adhesion molecule-1 mRNA levels was measured 2 h post-exposure followed at 6 h by upregulation of interleukin-1beta, interleukin-6, E-selectin, and intercellular adhesion molecule-1 with eventual resolution by 24-48 h. In conclusion, an acute and transient upregulation of the inflammatory gene response is activated following soman exposure that may be involved in the soman-induced brain injury process.
authors.affiliation: Walter Reed Army Institute of Research, Division of Neurosciences, Silver Spring, MD 20910, USA. spcanthony.williams@na.amedd.army.mil
authors.forename: A J
authors.initials: AJ
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: Berti
authors.forename: C
authors.initials: C
authors.lastname: Yao
authors.forename: R A
authors.initials: RA
authors.lastname: Price
authors.forename: L C
authors.initials: LC
authors.lastname: Velarde
authors.forename: I
authors.initials: I
authors.lastname: Koplovitz
authors.forename: S M
authors.initials: SM
authors.lastname: Schultz
authors.forename: F C
authors.initials: FC
authors.lastname: Tortella
authors.forename: J R
authors.initials: JR
authors.lastname: Dave
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002619:Chemical Warfare Agents / Q000633:toxicity*; D019040:E-Selectin / Q000235:genetics; D004660:Encephalitis / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012999:Soman / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D002619:Chemical Warfare Agents; D019040:E-Selectin; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D018727:Muscarinic Antagonists; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D001285:Atropine; D012999:Soman