title: Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice.
abstract: Activated microglia have been associated with neurodegeneration in patients and in animal models of Temporal Lobe Epilepsy (TLE), however their precise functions as neurotoxic or neuroprotective is a topic of significant investigation. To explore this, we examined the effects of pilocarpine-induced seizures in transgenic mice where microglia/macrophages were conditionally ablated. We found that unilateral ablation of microglia from the dorsal hippocampus did not alter acute seizure sensitivity. However, when this procedure was coupled with lipopolysaccharide (LPS) preconditioning (1 mg/kg given 24 h prior to acute seizure), we observed a significant pro-convulsant phenomenon. This effect was associated with lower metabolic activation in the ipsilateral hippocampus during acute seizures, and could be attributed to activity in the mossy fiber pathway. These findings reveal that preconditioning with LPS 24 h prior to seizure induction may have a protective effect which is abolished by unilateral hippocampal microglia/macrophage ablation.
authors.affiliation: Department of Pharmacological Sciences, Molecular and Cellular Pharmacology, Stony Brook University, Stony Brook, NY 11794-8651, USA.
authors.forename: Martine M
authors.initials: MM
authors.lastname: Mirrione
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Konomos
authors.forename: Iordanis
authors.initials: I
authors.lastname: Gravanis
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Dewey
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.forename: Stella E
authors.initials: SE
authors.lastname: Tsirka
mesh_terms: D000208:Acute Disease; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D010862:Pilocarpine / Q000008:administration & dosage*
chemical_list: D008070:Lipopolysaccharides; D010862:Pilocarpine
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