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Brain infiltration of leukocytes contributes to the pathophysiology of temporal lobe epilepsy.
MedLine Citation:
PMID:  21411646     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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) and CD3 (T-lymphocytes), we show here microglial activation and infiltration of leukocytes in sclerotic tissue from patients with mesial temporal lobe epilepsy (TLE), as well as in a model of TLE (intrahippocampal kainic acid injection), characterized by spontaneous, nonconvulsive focal seizures. Using specific markers of lymphocytes, microglia, macrophages, and neutrophils in kainate-treated mice, we investigated with pharmacological and genetic approaches the contribution of innate and adaptive immunity to kainate-induced inflammation and neurodegeneration. Furthermore, we used EEG analysis in mutant mice lacking specific subsets of lymphocytes to explore the significance of inflammatory processes for epileptogenesis. Blood-brain barrier disruption and neurodegeneration in the kainate-lesioned hippocampus were accompanied by sustained ICAM-1 upregulation, microglial cell activation, and infiltration of CD3(+) T-cells. Moreover, macrophage infiltration was observed, selectively in the dentate gyrus where prominent granule cell dispersion was evident. Unexpectedly, depletion of peripheral macrophages by systemic clodronate liposome administration affected granule cell survival. Neurodegeneration was aggravated in kainate-lesioned mice lacking T- and B-cells (RAG1-knock-out), because of delayed invasion by Gr-1(+) neutrophils. Most strikingly, these mutant mice exhibited early onset of spontaneous recurrent seizures, suggesting a strong impact of immune-mediated responses on network excitability. Together, the concerted action of adaptive and innate immunity triggered locally by intrahippocampal kainate injection contributes seizure-suppressant and neuroprotective effects, shedding new light on neuroimmune interactions in temporal lobe epilepsy.
Authors:
Michela Zattoni; Maria Luisa Mura; Francine Deprez; Reto A Schwendener; Britta Engelhardt; Karl Frei; Jean-Marc Fritschy
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  31     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4037-50     Citation Subset:  IM    
Affiliation:
Institute of Pharmacology and Toxicology and Institute of Molecular Cancer Research, University of Zurich, CH-8057 Zurich, Switzerland, Department of Neurosurgery, University Hospital Zurich, CH-8091 Zurich, Switzerland, and Theodor Kocher Institute, University of Bern, CH-3012 Bern, Switzerland.
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