LPS-induced neuroinflammatory effects do not recover with time.

Inflammatory processes develop in the vicinity of the neuropathological hallmarks associated with Alzheimer's disease (AD) and may play a role in the progression of the disease and its clinical expression. We have previously reported that chronic infusion of LPS into the fourth ventricle of rat brains reproduced many of the inflammatory and pathological changes seen in the brain of AD patients. In the current study, we used the same animal model to investigate the effects of longer infusion of LPS and whether these effects could recover over time. The results show that doubling the time of LPS infusion did not increase the inflammatory reaction and did not produce a significantly greater behavioral impairment. Waiting for 37 days after the cessation of the LPS infusion did not decrease the density of activated microglia and did not improve performances in the Morris water maze task. The results suggest that inflammation may contribute to the pathogenic mechanisms that underlie the clinical expression of AD.