A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-α and IL-18

Background: 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.methods: 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).results: 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.conclusions: 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. © 2012 bossù et al.; licensee biomed central ltd.