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Neurobiol Dis. 2010 Jul;39(1):85-97. doi: 10.1016/j.nbd.2010.04.001. Epub 2010 Apr 9.

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

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1
Department of Pharmacological Sciences, Molecular and Cellular Pharmacology, Stony Brook University, Stony Brook, NY 11794-8651, USA.

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.

PMID:
20382223
PMCID:
PMC2875881
DOI:
10.1016/j.nbd.2010.04.001
[Indexed for MEDLINE]
Free PMC Article
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