Role of microglial IKKb in kainic acid-induced hippocampal neuronal cell death

Microglial cells are activated during excitotoxin-induced neurodegeneration.However, the in vivo role of micro-glia activation in neurodegeneration has not yet been fully elucidated. To this end, we used Ikkb conditional knockoutmice (LysM-Cre/IkkbF/F) in which the Ikkb gene is specifically deleted in cells of myeloid lineage, includ-ing microglia, in the CNS. This deletion reduced IiB kinase (IKK) activity in cultured primary microglia by up to 40 % compared with wild-type (IkkbF/F), and lipopolysaccharide-induced proinflammatory gene expression was also compromised. Kainic acid (KA)-induced hippocampal neuronal cell death was reduced by 30 % in LysM-Cre/IkkbF/F mice compared with wild-type mice. Reduced neuronal cell death was accompanied by decreased KA-induced glial cell activation and subsequent expression of proinflammatory genes such as tumour necrosis factor (TNF)-a and interleukin (IL)-1b. Similarly, neurons in organotypic hippocampal slice cultures (OHSCs