Decrease of proinflammatory molecules correlates with neuroprotective effect of the fluorinated salicylate triflusal after postnatal excitotoxic damage

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Abstract

Background and Purpose - 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-1β (IL-1β), tumor necrosis factor-α (TNF-α), 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-1β, TNF-α, 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-1β, and TNF-α was observed. Triflusal decreased neuronal and microglial COX-2 expression at 10 and 24 hours after lesion and microglial and astroglial expression of IL-1β and TNF-α at 24 hours after lesion. TNF-α 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.
Original languageEnglish
Pages (from-to)2499-2505
JournalStroke
Volume33
DOIs
Publication statusPublished - 1 Oct 2002

Keywords

  • Astrocytes
  • Cyclooxygenase-2
  • Inflammation
  • Interleukins
  • Microglia
  • Nitric oxide synthase
  • Tumor necrosis factor

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