Brain Infiltration of Leukocytes Contributes to the Pathophysiology of Temporal Lobe Epilepsy

• DOI: 10.1523/jneurosci.6210-10.2011
• Publication Date: 2011-03-16T17:24:43Z
• Authors: Michela Zattoni; Maria Luisa Mura; Francine Deprez; Reto A. Schwendener; Britta Engelhardt; Karl Frei; Jean-Marc Fritschy
• Keywords: Kainate receptor

Clinical and experimental evidence indicates that inflammatory processes contribute to the pathophysiology of epilepsy, but underlying mechanisms remain mostly unknown. Using immunohistochemistry for CD45 (common leukocyte antigen) CD3 (T-lymphocytes), we show here microglial activation infiltration leukocytes in sclerotic tissue from patients with mesial temporal lobe epilepsy (TLE), as well a model TLE (intrahippocampal kainic acid injection), characterized by spontaneous, nonconvulsive focal seizures. specific markers lymphocytes, microglia, macrophages, neutrophils kainate-treated mice, investigated pharmacological genetic approaches contribution innate adaptive immunity kainate-induced inflammation neurodegeneration. Furthermore, used EEG analysis mutant mice lacking subsets lymphocytes explore significance epileptogenesis. Blood–brain barrier disruption neurodegeneration kainate-lesioned hippocampus were accompanied sustained ICAM-1 upregulation, cell activation, + T-cells. Moreover, macrophage was observed, selectively dentate gyrus where prominent granule dispersion evident. Unexpectedly, depletion peripheral macrophages systemic clodronate liposome administration affected survival. Neurodegeneration aggravated T- B-cells (RAG1-knock-out), because delayed invasion Gr-1 neutrophils. Most strikingly, these exhibited early onset spontaneous recurrent seizures, suggesting strong impact immune-mediated responses on network excitability. Together, concerted action triggered locally intrahippocampal kainate injection contributes seizure-suppressant neuroprotective effects, shedding new light neuroimmune interactions epilepsy.