Dexibuprofen (S(+)-isomer ibuprofen) reduces microglial activation and impairments of spatial working memory induced by chronic lipopolysaccharide infusion
Dexibuprofen (S(+)-isomer ibuprofen) reduces microglial activation and impairments of spatial working memory induced by chronic lipopolysaccharide infusion
复制标题
DOI：
10.1016/j.pbb.2008.01.016
复制
发表时间：
2008-05-01
影响因子：
3.6
通讯作者：
Han, Jung-Soo
中科院分区：
文献类型：
--
作者：
Jin, Da-Qing;Sung, Jin-Young;Han, Jung-Soo
非甾体抗炎药（NSAIDs）已被提议作为降低阿尔茨海默病（AD）风险的治疗药物。目前的研究表明，外周给药地塞米松（S（+）-异构体布洛芬），其引起的胃损伤较小，抗炎作用优于布洛芬，减少了皮质和海马中的小胶质细胞活化，并减少了海马中细胞外信号调节激酶的磷酸化，用脂多糖（LPS）慢性注入Wistar大鼠第四脑室，诱发脑缺血。在水迷宫中，用一个试验唯一的匹配位置任务来测量dexiblide对LPS输注诱导的空间工作记忆障碍的影响，该任务评估了不同延迟时间内位置信息的记忆。在水迷宫实验中，注射LPS的大鼠相对于注射人工脑脊液的大鼠表现出空间工作记忆障碍。每日给予地塞米松可降低慢性LPS输注引起的空间工作记忆障碍。结果表明，使用地塞米松的NSAID治疗显著减弱了驱动与AD相关的病理学的过程，并且该过程可能涉及抑制小胶质细胞活化。(c)2008年爱思唯尔公司All rights reserved.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been proposed as a therapeutics to reduce the risk of Alzheimer's disease (AD). The present study shows that the peripheral administration of dexibuprofen (S(+)-isomer ibuprofen), which causes less gastric damage and has better anti-inflammatory effects than ibuprofen, reduces the microglial activation in the cortex and hippocampus, and reduces the phosphorylation of extracellular signal-regulated kinases in the hippocampus, which has been induced by chronic infusion of lipopolysaccharide (LPS) into the fourth ventricle of Wistar rats. The effects of dexibuprofen on impairments of spatial working memory induced by LPS infusions were measured with a trial-unique matching-to-place task in a water maze which assessed memory for place information over varying delays. When performing the water maze task, the rats with the LPS infusions showed spatial working memory impairments relative to the rats with the artificial cerebrospinal fluid. Daily administrations of dexibuprofen reduced the spatial working memory impairment induced by the chronic LPS infusion. The results indicate that NSAID treatments using dexibuprofen significantly attenuate the processes that drive the pathology associated with AD and that this process may involve the suppression of microglial activation. (c) 2008 Elsevier Inc. All rights reserved.