Kainic acid-induced microglial activation is attenuated in aged interleukin-18 deficient mice

Background: previously,we found that interleukin (il)-18 deficiency aggravates kainic acid (ka)-induced hippocampal neurodegeneration in young c57bl/6 mice due to an over-compensation by il-12. additionally,il-18 participates in fundamental inflammatory processes that increase during aging. in the present study,we were interested in the role of il-18 in ka-induced neurodegeneration in aged female c57bl/6 mice.methods: fifteen aged female il-18 knockout (ko) and 15 age-matched wild-type (wt) mice (18 to 19 months old) were treated with ka at a dose of 25 mg/kg body weight intranasally. seizure activities and behavioral changes were rated using a 6-point scoring system and open-field test,respectively. seven days after ka treatment,degenerating neurons were detected by nissl's method and fluoro-jade b staining; and microglial activation was analyzed by immunohistochemistry and flow cytometry.results: aged female il-18 ko and wt mice showed similar responses to treatment with ka as demonstrated by comparable seizure activities,behavioral changes and neuronal cell death. however,aged female il-18 ko mice failed to exhibit the strong microglial activation shown in wt mice. interestingly,even though the number of activated microglia was less in ka-treated il-18 ko mice than in ka-treated wt mice,the proportion of microglia that expressed the cytokines tumor necrosis factor (tnf)-α,il-6 and il-10 was higher in ka-treated il-18 ko mice.conclusion: deficiency of il-18 attenuates microglial activation after ka-induced excitotoxicity in aged brain,while the net effects of il-18 deficiency are balanced by the enhancement of other cytokines,such as tnf-α,il-6 and il-10. © 2010 zhang et al; licensee biomed central ltd.