Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice

NEUROBIOLOGY OF DISEASE

卷:39

Article

Mirrione, Martine M.^1,2  Konomos, Dorothy K.¹  Gravanis, Iordanis¹  Dewey, Stephen L.^1,2,3  Aguzzi, Adriano⁴  Heppner, Frank L.^4,5  Tsirka, Stella E.¹ 

[1] SUNY Stony Brook, Dept Pharmacol Sci Mol & Cellular Pharmacol, Stony Brook, NY 11794 USA

[2] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA

[3] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA

[4] Univ Zurich Hosp, Inst Neuropathol, CH-8091 Zurich, Switzerland

[5] Charite, Dept Neuropathol, D-10117 Berlin, Germany

关键词: Microglia;    Seizure;    Epilepsy;    Lipopolysaccharide;    Status epilepticus;    Glucose;    Metabolism;    Positron emission tomography;    Pilocarpine;    Inflammation;    Mouse;    FDG;    Imaging;    Immune system;   

DOI  :  10.1016/j.nbd.2010.04.001

来源: Elsevier

【 摘 要 】

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. (C) 2010 Elsevier Inc. All rights reserved.

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