Abstracts

Inflammatory mediators are rapidly synthesized by glia and neurons in the rodent brain during seizures. The proinflammatory cytokine interleukin(IL)1beta increases epileptic activity and contributes to neurodegeneration. The aim of this study was to explore the relative contribution of innate and adaptive immune mechanisms in perpetuating brain inflammation during epileptogenesis and in the chronic phase of spontaneous seizures (SS)., The immunohistochemical pattern of microglia (CD-11b/c, HLA-DR), monocytes/macrophages (ED-1, CD68), granulocytes (HIS48), T-(CD3, CD4, CD8) and B-lymphocytes (CD45RA), NK (NKR-P1A) was assessed in rats, 4-36h (acute phase) and 3-7d (epileptogenesis) after the onset of pilocarpine-induced status epilepticus (SE) and during SS, and in hippocampal specimens from medically intractable TLE with or without hippocampal sclerosis (HS)., Activated IL-1beta-expressing microglia and astrocytes were observed in rat forebrain within 4h after SE while abundant parenchymal macrophages were found after 18h. Both cell populations persisted until SS. Granulocytes appeared between 18h-3d only. Scarse B and T-lymphocytes and NK cells were found associated with microvessels, rarely in brain parenchyma. No changes occurred in pilocarpine+phenobarbital treated rats. In human TLE with HS, IL-1beta-expressing microglia and astrocytes, and clusters of perivascular monocytes/macrophages occurred in the hippocampus; T-lymphocytes were scarse and B cells were lacking., Activated glial cells expressing IL-1beta sustain the early phases of inflammation after SE and, toghether with macrophages, contribute to its persistence both in rat and human epileptic tissue. Granulocytes are transiently recruited, while B-, T-, NK-cells are scarse or absent. These findings, together with functional studies in experimental models, indicate that innate, but not adaptive, immunity significantly contributes to epileptogenesis in TLE., (Supported by Fondazione Mariani Onlus and Negri-Weizmann Programme (A.V.) and National Epilepsy Fund (E.A., K.B.))