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(Stroke. 2001;32:2394.)
© 2001 American Heart Association, Inc.

Original Contributions

Triflusal Posttreatment Inhibits Glial Nuclear Factor-B, Downregulates the Glial Response, and Is Neuroprotective in an Excitotoxic Injury Model in Postnatal Brain

Laia Acarin, PhD; Berta González, PhD Bernardo Castellano, PhD

From the Unit of Histology, School of Medicine, Department of Cell Biology, Physiology, and Immunology, Autonomous University of Barcelona, Bellaterra, Spain.

Correspondence to Laia Acarin, PhD, Unitat Histologia, Facultat Medicina, Torre M5, Universitat Autònoma Barcelona, Bellaterra 08193, Spain. E-mail lacarin{at}servet.uab.es

Background and Purpose—— Nuclear factor-B (NF-B) and the signal transducer and activator of transcription 3 (STAT3) are important transcription factors regulating inflammatory mechanisms and the glial response to neural injury, determining lesion outcome. In this study we evaluate the ability of triflusal (2-acetoxy-4-trifluoromethylbenzoic acid), an antiplatelet agent inhibitor of NF-B activation, to improve lesion outcome after excitotoxic damage to the immature brain.

Methods—— Postnatal day 9 rats received an intracortical injection of the excitotoxin N-methyl-D-aspartate (NMDA) and oral administration of triflusal (30 mg/kg) either as 3 doses before NMDA injection (pretreatment) or as a single dose 8 hours after NMDA injection (posttreatment). After survival times of 10 and 24 hours, brains were processed for toluidine blue staining, tomato lectin histochemistry, and glial fibrillary acidic protein, NF-B, and STAT3 immunocytochemistry.

Results—— NMDA-lesioned animals that were not treated with triflusal showed activation of NF-B in neuronal cells at first and in glial cells subsequently. Animals that received pretreatment with triflusal showed a strong downregulation of neuronal and glial NF-B but a similar development of the glial response and an equivalent lesion volume compared with nontreated animals. In contrast, animals receiving triflusal posttreatment showed increased early neuronal NF-B but a reduction in the subsequent glial NF-B, accompanied by important downregulation of the microglial and astroglial response and a drastic reduction in the lesion size. STAT3 activation was not affected by triflusal treatment.

Conclusions—— Triflusal posttreatment diminishes glial NF-B, downregulates the glial response, and improves the lesion outcome, suggesting a neuroprotective role of this compound against excitotoxic injury in the immature brain.

Key Words: anti-inflammatory agents, nonsteroidal • antiplatelet agents • astrocytes • excitotoxicity • microglia • neuroglia • neuroprotection • newborn • salicylates • stroke, experimental • transcription factors

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