title: Combustion smoke-induced inflammation in the cerebellum and hippocampus of adult rats.
abstract: OBJECTIVE
  The effect of combustion smoke inhalation on the respiratory system is widely reported but its effects on the central nervous system remain unclear. Here, we aimed to determine the effects of smoke inhalation on the cerebellum and hippocampus which are areas vulnerable to hypoxia injury.
  
  
  METHODS
  Adult male Sprague-Dawley rats were subjected to combustion smoke inhalation and sacrificed at 0.5, 3, 24 and 72 h after exposure. The cerebellum and hippocampus were subjected to Western analysis for VEGF, iNOS, eNOS, nNOS and AQP4 expression; ELISA analysis for cytokine and chemokine levels; and immunohistochemistry for GFAP/AQP4, RECA-1/RITC and TUNEL. Aminoguanidine (AG) was administered to determine the effects of iNOS after smoke inhalation.
  
  
  RESULTS
  Both the cerebellum and hippocampus showed a significant increase in VEGF, iNOS, eNOS, nNOS and AQP4 expression with corresponding increases in inflammatory cytokines and chemokines and increased AQP4 expression and RITC permeability after smoke exposure. AG was able to decrease the expression of iNOS, followed by VEGF, eNOS, nNOS, RITC and AQP4 after smoke exposure. There was also a significant increase in TUNEL+ cells in the cerebellum and hippocampus which were not significantly reduced by AG. Beam walk test revealed immediate deficits after smoke inhalation which was attenuated with AG.
  
  
  CONCLUSIONS
  The findings suggest that iNOS plays a major role in the central nervous system inflammatory pathophysiology after smoke inhalation exposure with concomitant increase in proinflammatory molecules, vascular permeability and oedema, for which the cerebellum appears to be more vulnerable to smoke exposure than the hippocampus.
authors.affiliation: Department of Pathology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, China.
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Zou
authors.forename: E M
authors.initials: EM
authors.lastname: Kan
authors.forename: Q
authors.initials: Q
authors.lastname: Cao
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: E-A
authors.initials: EA
authors.lastname: Ling
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051401:Aquaporin 4; D012906:Smoke; D042461:Vascular Endothelial Growth Factor A; D019001:Nitric Oxide Synthase
keywords: brain oedema; cerebellum; hippocampus; inflammation; nitric oxide synthase; smoke