title: Uric acid is released in the brain during seizure activity and increases severity of seizures in a mouse model for acute limbic seizures.
abstract: Recent evidence points at an important role of endogenous cell-damage induced pro-inflammatory molecules in the generation of epileptic seizures. Uric acid, under the form of monosodium urate crystals, has shown to have pro-inflammatory properties in the body, but less is known about its role in seizure generation. This study aimed to unravel the contribution of uric acid to seizure generation in a mouse model for acute limbic seizures. We measured extracellular levels of uric acid in the brain and modulated them using complementary pharmacological and genetic tools. Local extracellular uric acid levels increased three to four times during acute limbic seizures and peaked between 50 and 100 min after kainic acid infusion. Manipulating uric acid levels through administration of allopurinol or knock-out of urate oxidase significantly altered the number of generalized seizures, decreasing and increasing them by a twofold respectively. Taken together, our results consistently show that uric acid is released during limbic seizures and suggest that uric acid facilitates seizure generalization.
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, De Pintelaan 185, 2 Blok B, 9000 Ghent, Belgium. Electronic address: Lisa.Thyrion@UGent.be.
authors.forename: Lisa
authors.initials: L
authors.lastname: Thyrion
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, De Pintelaan 185, 2 Blok B, 9000 Ghent, Belgium. Electronic address: Robrecht.Raedt@UGent.be.
authors.forename: Robrecht
authors.initials: R
authors.lastname: Raedt
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, De Pintelaan 185, 2 Blok B, 9000 Ghent, Belgium; Center for Neurosciences C4N, Department of Pharmaceutical Chemistry, Drug Analysis & Drug Information, Vrije Universiteit Brussel, Building G, Room G.103, Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: Jeanelle.Portelli@UGent.be.
authors.forename: Jeanelle
authors.initials: J
authors.lastname: Portelli
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, De Pintelaan 185, 2 Blok B, 9000 Ghent, Belgium. Electronic address: Pieter.VanLoo@uzgent.be.
authors.forename: Pieter
authors.initials: P
authors.lastname: Van Loo
authors.affiliation: Swammerdam Institute of Life Sciences, University of Amsterdam, Sciencepark 904, 1098 XH Amsterdam, The Netherlands. Electronic address: W.J.Wadman@Uva.nl.
authors.forename: Wytse J
authors.initials: WJ
authors.lastname: Wadman
authors.affiliation: Nephrology Section, Department of Internal Medicine, Ghent University Hospital, De Pintelaan 185, 0K12, 9000 Ghent, Belgium. Electronic address: Griet.Glorieux@UGent.be.
authors.forename: Griet
authors.initials: G
authors.lastname: Glorieux
authors.affiliation: Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, 'Fiers-Schell-Van Montagu' Building, Technologiepark 927, Zwijnaarde, 9052 Ghent, Belgium; Department of Internal Medicine, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands. Electronic address: Bart.Lambrecht@irc.vib-ugent.be.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, 'Fiers-Schell-Van Montagu' Building, Technologiepark 927, Zwijnaarde, 9052 Ghent, Belgium; Department of Internal Medicine, Ghent University, Ghent, Belgium. Electronic address: Sophie.Janssens@irc.vib-ugent.be.
authors.forename: Sophie
authors.initials: S
authors.lastname: Janssens
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, De Pintelaan 185, 2 Blok B, 9000 Ghent, Belgium. Electronic address: Kristl.Vonck@UGent.be.
authors.forename: Kristl
authors.initials: K
authors.lastname: Vonck
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, De Pintelaan 185, 2 Blok B, 9000 Ghent, Belgium. Electronic address: Paul.Boon@UGent.be.
authors.forename: Paul
authors.initials: P
authors.lastname: Boon
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid / Q000633:toxicity; D008032:Limbic System / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012640:Seizures / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors; D014503:Urate Oxidase / Q000172:deficiency / Q000235:genetics; D014527:Uric Acid / Q000378:metabolism*; D014741:Video Recording
chemical_list: D018690:Excitatory Amino Acid Agonists; D014527:Uric Acid; D014503:Urate Oxidase; D007608:Kainic Acid
keywords: Acute limbic seizures; Allopurinol; Kainic acid; Urate oxidase; Uric acid; Video-EEG