Fourteen days after chronic intracerebroventricular infusion of LPS in rats, an altered state of neuronal plasticity and an elevated number of OX-6 positive microglial cells were observed in the hippocampus. Co-administration of 3,6′-dithiothalidomide suppressed these effects of LPS. (A) After 14 days co-administration of LPS (i.c.v. ) with 3,6′-dithiothalidomide (i.p), no differences in the time spent in the outer and inner zone of an exploration chamber were observed between the treatment groups. In each animal cohort the rodents displayed a preference for the outer zone rather than the inner zone. The mean time spent in the two zones over the first 3 min of a 10-min exploratory period is shown (aCSF + Veh n = 1; n = 4–9). (B) The effects of the 10-min behavioral assessment on the immediate early gene. Activity regulated cytoskeletal protein (Arc) gene expression in the upper blade of the hippocampal neurons is presented; in situ hybridization data indicate that there was an increase in the number of neurons expressing Arc mRNA in LPS + vehicle-treated animals. The behavior-LPS-induced elevation was prevented by treatment with 3,6′-dithiothalidomide (n = 4–9). See Figure 3 for representative images of Arc staining. (C) LPS administration induced a significant increase in numbers of OX-6 positive microglial cells, while treatment with 3,6′-dithiothalidomide prevented this effect of LPS. See Figure 4 for representative images of activated microglia staining. Data are expressed as mean ± SEM of n observations; levels of statistical significance are indicated as follows: *P < 0.05.