Triflusal posttreatment inhibits glial nuclear factor-kappa B, downregulates the glial response, and is neuroprotective in an excitotoxic injury model in postnatal brain
L. Acarin et al., Triflusal posttreatment inhibits glial nuclear factor-kappa B, downregulates the glial response, and is neuroprotective in an excitotoxic injury model in postnatal brain, STROKE, 32(10), 2001, pp. 2394-2402
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.