Abstracts

Rationale: Immunomodulating treatments such as immunoglobulin and steroid therapies suggest a pathogenic role of neuro-inflammation for the initiation and exacerbation of seizures in chronic epilepsy. Brain inflammation is mainly induced and regulated by innate immune cells, such as microglia and astrocytes, and adaptive immune cells such as B and T lymphocytes. The role of macrophages/microglia as innate immune cells is well established, however their antigen presentation capability in terms of generation and progression of seizures remains controversial and exact profile of subsequent infiltrating adaptive immune cells into epileptic brain is not well understood. Here, we determined whether leukocytes infiltrate the brain of epileptic Kcna1-null (KO) mice and if there is evidence of a peripheral adaptive immune response.Methods: Fluorescence-activated cell sorting (FACS) analysis was used to determine the presence of lymphocytes (CD4+ T helper cells, CD8+ cytotoxic T cells and B220+ B cells), monocytes (macrophage Mac-1+ cells and microglia Mac-1+ cells), activated macrophages/microglia (Mac-1+ MHC-II+ cells) and granulocytes (neutrophils Gr-1+ cells) in isolated brain and spleen of wildtype (WT) and KO mice. In additional cohorts of mice, FACS analysis was run on regional dissections of cortical and hippocampal tissue.Results: In KO brain CD4+ T helper, CD8+ cytoxic T cells and Gr-1+ neutrophils were either significantly elevated or demonstrated strong trends toward elevation compared to WT brain. Upon regional inspection, CD4+ cells and Gr-1+ cells were enriched in hippocampal tissue compared to cortical tissue from KO brains. Levels of CD8+ cells were similar in both regions. In KO spleen CD8+ cells and Mac-1+ MHC-II+ activated macrophages/microglia were significantly increased, whereas B220+ B cells and Mac-1+ cells were reduced compared to WT.Conclusions: Our data indicate that the adaptive immune system is chronically activated in epileptic KO mice and infiltrates the brain. Future studies will determine whether adaptive immune cells participate in epileptogenesis, seizure-genesis or seizure worsening in this model of chronic epilepsy.