The protective effects of interleukin-18 and interferon-gamma on neuronal damages in the rat hippocampus following status epilepticus.

摘要

To elucidate whether interleukin-18 (IL-18) or interferon-gamma (IFN-gamma) participates in neurodegeneartion, we investigated the changes in IL-18 and IFN-gamma systems within the rat hippocampus following status epilepticus (SE). In non-SE induced animals, IL-18, IL-18 receptor alpha (IL-18Ralpha), IFN-gamma and IFN-gamma receptor alpha (IFN-gammaRalpha) immunoreactivity was not detected in the hippocampus. Following SE, IL-18 immunoreactivity was increased in CA1-3 pyramidal cells as well as dentate granule cells. IL-18 immunoreactivity was also up-regulated in astrocytes and microglia/macrophages. IL-18Ralpha immunoreactivity was detected in astrocytes and microglia/macrophages. IFN-gamma immunoreactivity was detected only in astrocytes within all regions of the hippocampus. IFN-gammaRalpha immunoreactivity was increased in neurons as well as astrocytes. Intracerebroventricular infusions of recombinant rat IL-18 or IFN-gamma alleviated SE-induced neuronal damages, while neutralization of IL-18, IFN-gamma or their receptors aggravated them, as compared to saline-infused animals. These findings suggest that astroglial-mediated IFN-gamma pathway in response to IL-18 induction may play an important role in alleviation of SE-induced neuronal damages.