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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:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
BROOKHAVEN NATIONAL LABORATORY (BNL)
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
989166
Report Number(s):
BNL-93920-2010-JA
Journal ID: ISSN 0969-9961; R&D Project: 07-096; MO-085; KP6002010; TRN: US201019%%376
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Neurobiology Of Disease; Journal Volume: 39; Journal Issue: 1
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; ABLATION; ANIMALS; EPILEPSY; FIBERS; HIPPOCAMPUS; INDUCTION; LIPOPOLYSACCHARIDES; METABOLIC ACTIVATION; MICE; PATIENTS; SENSITIVITY; TRANSGENIC MICE; microglial ablation; mice; seizures

Citation Formats

Mirrione, M.M., Mirrione, M.M., Konomosa, D.K., Ioradanis, G., Dewey, S.L., Agzzid, A., Heppnerd, F.L., and Tsirka, St.E. Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice. United States: N. p., 2010. Web. doi:10.1016/j.nbd.2010.04.001.
Mirrione, M.M., Mirrione, M.M., Konomosa, D.K., Ioradanis, G., Dewey, S.L., Agzzid, A., Heppnerd, F.L., & Tsirka, St.E. Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice. United States. doi:10.1016/j.nbd.2010.04.001.
Mirrione, M.M., Mirrione, M.M., Konomosa, D.K., Ioradanis, G., Dewey, S.L., Agzzid, A., Heppnerd, F.L., and Tsirka, St.E. 2010. "Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice". United States. doi:10.1016/j.nbd.2010.04.001.
@article{osti_989166,
title = {Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice},
author = {Mirrione, M.M. and Mirrione, M.M. and Konomosa, D.K. and Ioradanis, G. and Dewey, S.L. and Agzzid, A. and Heppnerd, F.L. and Tsirka, St.E.},
abstractNote = {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.},
doi = {10.1016/j.nbd.2010.04.001},
journal = {Neurobiology Of Disease},
number = 1,
volume = 39,
place = {United States},
year = 2010,
month = 4
}
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