Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice.
Publication/Presentation Date
7-1-2010
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.
Volume
39
Issue
1
First Page
85
Last Page
97
ISSN
1095-953X
Published In/Presented At
Mirrione, M. M., Konomos, D. K., Gravanis, I., Dewey, S. L., Aguzzi, A., Heppner, F. L., & Tsirka, S. E. (2010). Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice. Neurobiology of disease, 39(1), 85–97. https://doi.org/10.1016/j.nbd.2010.04.001
Disciplines
Medicine and Health Sciences
PubMedID
20382223
Department(s)
Department of Medicine
Document Type
Article