title: Decrease of proinflammatory molecules correlates with neuroprotective effect of the fluorinated salicylate triflusal after postnatal excitotoxic damage.
abstract: OBJECTIVE
  The fluorinated salicylate triflusal has been shown to have a neuroprotective effect after an excitotoxic lesion to the postnatal brain. In this regard, the aim of this study was to elucidate whether neuroprotection was associated with changes in the expression of proinflammatory molecules such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS), or cyclooxygenase-2 (COX-2), well-known mediators of oxidative stress and inflammation, mechanisms underlying secondary damage occurring after excitotoxic/ischemic brain injury.
  
  
  METHODS
  Postnatal day 9 rats received an intracortical injection of N-methyl-D-aspartate followed by oral administration of triflusal (30 mg/kg) 8 hours later. Ten or 24 hours after lesion, animals were killed, and brain sections processed for the immunohistochemical demonstration of IL-1beta, TNF-alpha, iNOS, and COX-2.
  
  
  RESULTS
  Besides a reduction in the neurodegenerative area, triflusal strongly decreased iNOS immunolabeling at both survival times analyzed, attenuating iNOS immunoreactivity in astroglial cells and infiltrated neutrophils. Additionally, a moderate reduction in COX-2, IL-1beta, and TNF-alpha was observed. Triflusal decreased neuronal and microglial COX-2 expression at 10 and 24 hours after lesion and microglial and astroglial expression of IL-1beta and TNF-alpha at 24 hours after lesion. TNF-alpha expression in neuronal cells at 10 hours after lesion was, however, maintained.
  
  
  CONCLUSIONS
  This study suggests that triflusal neuroprotection is associated with a decrease of iNOS and other inflammatory mediators and therefore may constitute a good therapeutic agent in pathological situations in which regulation of inflammatory genes constitutes a relevant step in the outcome of the neurodegenerative event.
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D051546:Cyclooxygenase 2; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D008845:Microinjections; D016202:N-Methylaspartate; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009498:Neurotoxins; D020556:Neutrophil Infiltration / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D012459:Salicylates / Q000008:administration & dosage*; D013003:Somatosensory Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D007375:Interleukin-1; D007527:Isoenzymes; D018696:Neuroprotective Agents; D009498:Neurotoxins; D012459:Salicylates; D014409:Tumor Necrosis Factor-alpha; C016167:triflusal; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases