Kainic acid-induced excitotoxic hippocampal neurodegeneration in C57BL/6 mice: B cell and T cell subsets may contribute differently to the pathogenesis

Abstract

The roles of T cells and B cells in kainic acid (KA)-induced hippocampal lesions were studied in C57BL/6 mice lacking specific T cell populations (CD4, CD8, and CD4/CD8 cells) and B cells [Igh-6(−/−)]. At 48 mg/kg of KA administrated intranasally, KA-induced convulsions were seen in all groups. However, CD4/CD8(−/−) mice exhibited the mildest seizures; the responses of CD8(−/−), Igh-6(−/−) and wild-type mice were intermediate, whereas CD4(−/−) mice displayed much more severe clinical signs and 100% early mortality, indicating that a deficiency of CD4 T cells obviously increased susceptibility to KA-induced brain damage. Histopathological analysis of the mice that survived 7 days after KA administration revealed that CD4/CD8(−/−) mice had the fewest pathologic changes but Igh-6(−/−) mice showed more severe lesions in area CA3 of the hippocampus than CD8(−/−) and wild-type mice. Reactive astrogliosis were prominent in all KA-treated mice. Locomotor activity as assessed by open-field test increased after KA administration in Igh-6(−/−) and wild-type mice only. These results denote the influence of the adaptive immune response on KA-induced hippocampal neurodegeneration and suggest that B cell and T cell subsets may contribute differently to the pathogenesis.