Repeated low-dose kainate administration in C57BL/6J mice produces temporal lobe epilepsy pathology but infrequent spontaneous seizures

• Published in: Experimental neurology Vol. 279; pp. 116 - 126
• Main Authors: Umpierre, Anthony D., Bennett, Isaiah V., Nebeker, Lismore D., Newell, Thomas G., Tian, Bruce B., Thomson, Kyle E., White, H. Steve, White, John A., Wilcox, Karen S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2016
• Subjects: Animals; Astrocytes - pathology; Astrogliosis; C57 (C57BL/6J); Cell death; Cell Death - drug effects; Disease Models, Animal; Electroencephalography; Epilepsy, Temporal Lobe - chemically induced; Epilepsy, Temporal Lobe - pathology; Excitatory Amino Acid Agonists - toxicity; Glial Fibrillary Acidic Protein - metabolism; Gliosis - chemically induced; Gliosis - pathology; Hippocampus - pathology; Kainate; Kainic Acid - toxicity; Male; mGluR5; Mice; Mice, Inbred C57BL; Neurodegeneration; Receptor, Metabotropic Glutamate 5 - biosynthesis; Seizure; Seizures - chemically induced; Status Epilepticus - chemically induced; Status Epilepticus - pathology; Temporal lobe epilepsy; Valproic acid; Astrogliosis; C57 (C57BL/6J); Kainate; Cell death; Neurodegeneration; Temporal lobe epilepsy; Seizure; Valproic acid; mGluR5
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2016.02.014

More efficient or translationally relevant approaches are needed to model acquired temporal lobe epilepsy (TLE) in genetically tractable mice. The high costs associated with breeding and maintaining transgenic, knock-in, or knock-out lines place a high value on the efficiency of induction and animal survivability. Herein, we describe our approaches to model acquired epilepsy in C57BL/6J mice using repeated, low-dose kainate (KA) administration paradigms. Four paradigms (i.p.) were tested for their ability to induce status epilepticus (SE), temporal lobe pathology, and the development of epilepsy. All four paradigms reliably induce behavioral and/or electrographic SE without mortality over a 7d period. Two of the four paradigms investigated produce features indicative of TLE pathology, including hippocampal cell death, widespread astrogliosis, and astrocyte expression of mGluR5, a feature commonly reported in TLE models. Three of the investigated paradigms were able to produce aberrant electrographic features, such as interictal spiking in cortex. However, only one paradigm, previously published by others, produces spontaneous recurrent seizures over an eight week period. Presentation of spontaneous seizures is rare (N=2/14), with epilepsy preferentially developing in animals having a high number of seizures during SE. Overall, repeated, low-dose KA administration improves the efficiency and pathological relevance of a systemic KA insult, but does not produce a robust epilepsy phenotype under the experimental paradigms described herein. •Low-dose kainate administration produces hippocampal and limbic cell death in C57 mice•Low-dose kainate administration results in reactive astrogliosis and the expression of mGluR5 on astrocytes•We determine, for the first time, the long-term impact of a systemic kainate insult in C57 mice using video EEG•Epilepsy development after kainate administration is rare and may require a higher seizure burden during status epilepticus