Triflusal posttreatment inhibits glial nuclear factor-κB, downregulates the glial response, and is neuroprotective in an excitotoxic injury model in postnatal brain
Triflusal posttreatment inhibits glial nuclear factor-κB, downregulates the glial response, and is neuroprotective in an excitotoxic injury model in postnatal brain
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DOI：
10.1161/hs1001.097243
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发表时间：
2001-10-01
期刊：
影响因子：
8.3
通讯作者：
Castellano, B
中科院分区：
文献类型：
--
作者：
Acarin, L;González, B;Castellano, B
背景和目的核因子-κ B（NF-κ B）和信号转导子和转录激活子3（STAT 3）是重要的转录因子，它们调节炎症机制和神经胶质对神经损伤的反应，决定损伤的结果。在这项研究中，我们评估了三氟柳的能力，（2-乙酰氧基-4-三氟甲基苯甲酸），一种NF-κ B活化的抗血小板剂抑制剂，方法出生后9天的大鼠接受皮质内注射兴奋性毒素N-甲基-D-天冬氨酸（NMDA）和口服三氟柳后，（30 mg/kg），在NMDA注射前作为3个剂量（预处理）或在NMDA注射后8小时作为单次剂量（处理后）。经过10和24小时的生存时间，大脑进行处理甲苯胺蓝染色，番茄凝集素组织化学，和神经胶质细胞酸性蛋白，NF-κ B，和STAT 3 immunocytochemical.Results-NMDA损伤的动物，没有与三氟柳治疗显示NF-κ B在神经元细胞中的激活，并在神经胶质细胞随后。接受三氟柳预处理的动物显示出神经元和神经胶质NF-κ B的强烈下调，但与未处理的动物相比，神经胶质反应的发展相似，病变体积相等。相比之下，接受三氟柳后处理的动物显示早期神经元NF-κ B增加，但随后的神经胶质细胞NF-κ B减少，伴随着小胶质细胞和星形胶质细胞反应的重要下调以及病变大小的急剧减少。STAT 3激活不受影响triflusal treatment. Conclusions-Triflusal后处理减少神经胶质细胞NF-κ B，下调神经胶质细胞的反应，并改善病变的结果，这表明这种化合物对兴奋性毒性损伤的神经保护作用在未成熟的大脑。
Background and Purpose-Nuclear factor-kappaB (NF-kappaB) 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-kappaB 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-kappaB, and STAT3 immunocytochemistry.Results-NMDA-lesioned animals that were not treated with triflusal showed activation of NF-kappaB 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-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 increased early neuronal NF-kappaB but a reduction in the subsequent glial NF-kappaB, 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-kappaB, downregulates the glial response, and improves the lesion outcome, suggesting a neuroprotective role of this compound against excitotoxic injury in the immature brain.