Hauss-Wegrzyniak B, Vraniak P, Wenk G L
Arizona Research Laboratories, Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, 85724, USA.
Neurobiol Aging. 1999 May-Jun;20(3):305-13. doi: 10.1016/s0197-4580(99)00028-7.
Chronic inflammation may play an important role in the pathogenesis of Alzheimer's disease (AD). The present study compared the effects of chronic neuroinflammation, produced by infusion of lipopolysaccharide (LPS) into the fourth ventricle, upon memory in young, adult, and old rats. Nonsteroidal anti-inflammatory drug (NSAID) therapy may delay the onset of AD. We show that NO-Flurbiprofen (NFP), a novel NSAID that lacks gastrointestinal side effects, attenuated the neuroinflammatory reaction and reduced the inflammation-induced memory deficit. Chronic LPS infusions impaired performance of young rats but not adult or old rats. Treatment with NFP improved the performance of LPS-infused young rats, but not LPS-infused adult or old rats. LPS infusions increased the number of activated microglia in young and adult rats but not old rats. NFP treatment attenuated the effects of LPS upon microglia activation in young and adult rats, but not old rats. The results suggest that NSAID therapies designed to influence the onset of AD should be initiated in adults before age-associated inflammatory processes within the brain have a chance to develop.
慢性炎症可能在阿尔茨海默病（AD）的发病机制中起重要作用。本研究比较了通过向第四脑室注入脂多糖（LPS）产生的慢性神经炎症对年轻、成年和老年大鼠记忆的影响。非甾体抗炎药（NSAID）治疗可能会延迟AD的发病。我们发现，新型无胃肠道副作用的NSAID——NO-氟比洛芬（NFP）可减轻神经炎症反应，并减少炎症诱导的记忆缺陷。慢性注入LPS会损害年轻大鼠的行为表现，但对成年或老年大鼠无影响。用NFP治疗可改善注入LPS的年轻大鼠的行为表现，但对注入LPS的成年或老年大鼠无改善作用。注入LPS会增加年轻和成年大鼠而非老年大鼠中活化小胶质细胞的数量。NFP治疗可减轻LPS对年轻和成年大鼠小胶质细胞活化的影响，但对老年大鼠无此作用。结果表明，旨在影响AD发病的NSAID治疗应在成年人中进行，此时大脑中与年龄相关的炎症过程尚未有机会发展。
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