title: Increased expression of the chemokines CXCL1 and MIP-1α by resident brain cells precedes neutrophil infiltration in the brain following prolonged soman-induced status epilepticus in rats.
abstract: BACKGROUND
  Exposure to the nerve agent soman (GD) causes neuronal cell death and impaired behavioral function dependent on the induction of status epilepticus (SE). Little is known about the maturation of this pathological process, though neuroinflammation and infiltration of neutrophils are prominent features. The purpose of this study is to quantify the regional and temporal progression of early chemotactic signals, describe the cellular expression of these factors and the relationship between expression and neutrophil infiltration in damaged brain using a rat GD seizure model.
  
  
  METHODS
  Protein levels of 4 chemokines responsible for neutrophil infiltration and activation were quantified up to 72 hours in multiple brain regions (i.e. piriform cortex, hippocampus and thalamus) following SE onset using multiplex bead immunoassays. Chemokines with significantly increased protein levels were localized to resident brain cells (i.e. neurons, astrocytes, microglia and endothelial cells). Lastly, neutrophil infiltration into these brain regions was quantified and correlated to the expression of these chemokines.
  
  
  RESULTS
  We observed significant concentration increases for CXCL1 and MIP-1α after seizure onset. CXCL1 expression originated from neurons and endothelial cells while MIP-1α was expressed by neurons and microglia. Lastly, the expression of these chemokines directly preceded and positively correlated with significant neutrophil infiltration in the brain. These data suggest that following GD-induced SE, a strong chemotactic response originating from various brain cells, recruits circulating neutrophils to the injured brain.
  
  
  CONCLUSIONS
  A strong induction of neutrophil attractant chemokines occurs following GD-induced SE resulting in neutrophil influx into injured brain tissues. This process may play a key role in the progressive secondary brain pathology observed in this model though further study is warranted.
authors.affiliation: Research Division, Pharmacology Branch, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA. erik.a.johnson1@us.army.mil
authors.forename: Erik A
authors.initials: EA
authors.lastname: Johnson
authors.forename: Thuy L
authors.initials: TL
authors.lastname: Dao
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Guignet
authors.forename: Claire E
authors.initials: CE
authors.lastname: Geddes
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Koemeter-Cox
authors.forename: Robert K
authors.initials: RK
authors.lastname: Kan
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D054405:Chemokine CCL3 / Q000276:immunology*; D054360:Chemokine CXCL1 / Q000276:immunology*; D003292:Convulsants / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology; D007118:Immunoassay / Q000379:methods; D008297:Male; D017628:Microglia / Q000166:cytology / Q000276:immunology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012999:Soman / Q000494:pharmacology*; D013226:Status Epilepticus / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D054405:Chemokine CCL3; D054360:Chemokine CXCL1; D003292:Convulsants; D012999:Soman