title: Combustion smoke-induced inflammation in the olfactory bulb of adult rats.
abstract: BACKGROUND
  The damaging effect of combustion smoke inhalation on the lung is widely reported but information on its effects on the olfactory bulb is lacking. This study sought to determine the effects of smoke inhalation on the olfactory bulb, whose afferent input neurons in the nasal mucosa are directly exposed to external stimuli, such as smoke.
  
  
  METHODS
  Adult male Sprague-Dawley rats were subjected to combustion smoke inhalation and sacrificed at different time points. Changes in olfactory bulb proteins including vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), Na+-K+-Cl- cotransporter 1 (NKCC1), glial fibrillary acidic protein (GFAP), and aquaporin-4 (AQP4) were evaluated by Western blot analysis. In addition, ELISA was conducted for cytokine and chemokine levels, and double immunofluorescence labeling was carried out for GFAP/VEGF, GFAP/AQP4, NeuN/nNOS, GFAP/NKCC1, NeuN/NKCC1, GFAP/Rhodamine isothiocyanate (RITC), and transferase dUTP nick end labeling (TUNEL). Aminoguanidine was administered to determine the effects of iNOS inhibition on the targets probed after smoke inhalation.
  
  
  RESULTS
  The results showed a significant increase in VEGF, iNOS, eNOS, nNOS, NKCC1, and GFAP expression in the bulb tissues, with corresponding increases in inflammatory cytokines and chemokines after smoke inhalation. Concurrent to this was a drastic increase in AQP4 expression and RITC permeability. Aminoguanidine administration decreased the expression of iNOS and RITC extravasation after smoke inhalation. This was coupled with a significant reduction in incidence of TUNEL + cells that was not altered with administration of L-NG-nitroarginine methyl ester (L-NAME).
  
  
  CONCLUSIONS
  These findings suggest that the upregulation of iNOS in response to smoke inhalation plays a major role in the olfactory bulb inflammatory pathophysiology, along with a concomitant increase in pro-inflammatory molecules, vascular permeability, and edema. Overall, these findings indicate that the olfactory bulb is vulnerable to smoke inhalation.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zou
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
authors.forename: Enci Mary
authors.initials: EM
authors.lastname: Kan
authors.forename: Jia
authors.initials: J
authors.lastname: Lu
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016207:Cytokines / Q000032:analysis; D005455:Fluorescent Antibody Technique; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009830:Olfactory Bulb / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D012906:Smoke