Clinical and Behavioral Neurology, IRCCS Fondazione Santa Lucia, Via Ardeatina 30600179, Rome, Italy.
J Neuroinflammation. 2012 May 29;9:101. doi: 10.1186/1742-2094-9-101.
Systemic inflammation might cause neuronal damage and sustain neurodegenerative diseases and behavior impairment, with the participation of pro-inflammatory cytokines, like tumor necrosis factor (TNF)-α and interleukin (IL)-18. However, the potential contribution of these cytokines to behavioral impairment in the long-term period has not been fully investigated.
Wistar rats were treated with a single intraperitoneal injection of LPS (5 mg/kg) or vehicle. After 7 days and 10 months, the animal behavior was evaluated by testing specific cognitive functions, as mnesic, discriminative, and attentional functions, as well as anxiety levels. Contextually, TNF-α and IL-18 protein levels were measured by ELISA in defined brain regions (that is, frontal cortex, hippocampus, striatum, cerebellum, and hypothalamus).
Behavioral testing demonstrated a specific and persistent cognitive impairment characterized by marked deficits in reacting to environment modifications, possibly linked to reduced motivational or attentional deficits. Concomitantly, LPS induced a TNF-α increase in the hippocampus and frontal cortex (from 7 days onward) and cerebellum (only at 10 months). Interestingly, LPS treatment enhanced IL-18 expression in these same areas only at 10 months after injection.
Overall, these results indicate that the chronic neuroinflammatory network elicited by systemic inflammation involves a persistent participation of TNF-α accompanied by a differently regulated contribution of IL-18. This leads to speculation that, though with still unclear mechanisms, both cytokines might take part in long-lasting modifications of brain functions, including behavioral alteration.
全身性炎症可能会导致神经元损伤，并通过促炎细胞因子（如肿瘤坏死因子 (TNF)-α 和白细胞介素 (IL)-18）参与维持神经退行性疾病和行为损伤。然而，这些细胞因子是否会对长期行为损伤产生潜在影响尚未得到充分研究。
Wistar 大鼠接受单次腹腔注射 LPS（5mg/kg）或载体。7 天后和 10 个月后，通过测试特定的认知功能（如记忆、辨别和注意力功能）以及焦虑水平来评估动物行为。同时，通过 ELISA 测量特定脑区（即额叶皮质、海马体、纹状体、小脑和下丘脑）中 TNF-α 和 IL-18 的蛋白水平。
行为测试表明存在特定且持久的认知障碍，其特征是对环境变化的反应明显减少，这可能与动机或注意力缺陷有关。同时，LPS 在海马体和额叶皮质（从 7 天开始）以及小脑（仅在 10 个月时）引起 TNF-α 的增加。有趣的是，LPS 处理仅在注射后 10 个月增强了这些相同区域中 IL-18 的表达。
总体而言，这些结果表明全身性炎症引起的慢性神经炎症网络涉及 TNF-α 的持续参与，同时 IL-18 的参与受到不同的调节。这使得人们推测，尽管机制尚不清楚，但这两种细胞因子可能参与了包括行为改变在内的大脑功能的持久改变。
