Increasing clinical and experimental evidence links immune and inflammatory 
alterations with the pathogenesis of autism spectrum disorders (ASD). Autistic 
individuals show signs of neuroinflammation, altered inflammatory responses, and 
immune abnormalities throughout life. Mice injected subcutaneously with 600 
mg/kg valproic acid (VPA600) at gestational day 12.5 show reduced social 
interaction in adulthood (at 8 weeks of age), and they have been proposed as a 
mouse model of autism. Here, we show that these adult animals present signs of 
chronic glial activation in the hippocampus and the cerebellum. Moreover, when 
they are challenged with a peripheral inflammatory stimulus (intraperitoneal 
lipopolysaccharides, LPS), VPA600 animals show an exacerbated inflammatory 
response. Two hours after LPS injection, VPA600 animals secrete more 
corticosterone to the blood than control mice, and show an increase in the 
levels of expression of proinflammatory cytokines in the spleen. After LPS 
challenge, VPA600 mice also show signs of increased neuroinflammation compared 
with control mice: they have more microglial cells in the hippocampus, and they 
show higher levels of proinflammatory cytokines in the cerebellum. Our results 
provide evidence of basal neuroinflammation and an altered inflammatory response 
in the VPA model of autism. We propose that this model can be used to evaluate 
the contribution of inflammatory reactivity to autism-related behaviors. These 
studies will contribute to elucidate the role of the inflammatory alterations 
observed in ASD individuals.