Triflusal posttreatment inhibits glial nuclear factor-kappa B, downregulates the glial response, and is neuroprotective in an excitotoxic injury model in postnatal brain

Background and Purpose-Nuclear factor-kappaB (NF-kappaB) and the signal tra nsducer and activator of transcription 3 (STAT3) are important transcriptio n factors regulating inflammatory mechanisms and the glial response to neur al injury, determining lesion outcome. In this study we evaluate the abilit y of triflusal (2-acetoxy-4-trifluoromethylbenzoic acid), an antiplatelet a gent inhibitor of NF-kappaB activation, to improve lesion outcome after exc itotoxic damage to the immature brain. Methods-Postnatal day 9 rats received an intracortical injection of the exc itotoxin N-methyl-D-aspartate (NMDA) and oral administration of triflusal ( 30 mg/kg) either as 3 doses before NMDA injection (pretreatment) or as a si ngle dose 8 hours after NMDA injection (posttreatment). After survival time s of 10 and 24 hours, brains were processed for toluidine blue staining, to mato lectin histochemistry, and glial fibrillary acidic protein, NF-kappaB, and STAT3 immunocytochemistry. Results-NMDA-lesioned animals that were not treated with triflusal showed a ctivation of NF-kappaB in neuronal cells at first and in glial cells subseq uently. Animals that received pretreatment with triflusal showed a strong d ownregulation of neuronal and glial NF-kappaB but a similar development of the glial response and an equivalent lesion volume compared with nontreated animals. In contrast, animals receiving triflusal posttreatment showed inc reased early neuronal NF-kappaB but a reduction in the subsequent glial NF- kappaB, accompanied by important downregulation of the microglial and astro glial response and a drastic reduction in the lesion size. STAT3 activation was not affected by triflusal treatment. Conclusions-Triflusal posttreatment diminishes glial NF-kappaB, downregulat es the glial response, and improves the lesion outcome, suggesting a neurop rotective role of this compound against excitotoxic injury in the immature brain.