Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/121186
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Type: Journal article
Title: Hippocampal volume and cell density changes in a mouse model of human genetic epilepsy
Author: Richards, K.L.
Kurniawan, N.D.
Yang, Z.
Kim, T.H.
Keller, M.D.
Low, J.
Ullmann, J.F.
Cole, S.
Foong, S.
Galloway, G.J.
Reid, C.A.
Paxinos, G.
Reutens, D.C.
Petrou, S.
Citation: Neurology, 2013; 80(13):1240-1246
Publisher: American Academy of Neurology
Issue Date: 2013
ISSN: 0028-3878
1526-632X
Statement of
Responsibility: 
Kay L. Richards, Nyoman D. Kurniawan, Zhengyi Yang, Tae Hwan Kim, Marianne D. Keller, Jun Low ... et al.
Abstract: OBJECTIVE: The human γ-aminobutyric acid type A (GABAA)γ2R43Q (R43Q) mutation is associated with genetic epilepsy with febrile seizures. R43Q mice in the C57Bl/6J background do not display spontaneous seizures, but are significantly more susceptible to hyperthermic seizures, providing a model with enhanced seizure susceptibility without the confounding influence of ongoing epileptic activity. Because of GABA's role in brain development, we sought to determine whether the R43Q mutation alters brain structure before the appearance of seizures. METHODS: We used 16.4-tesla, high-field MRI to determine the volumes of hippocampal subregions. Histologic analysis of the same brains allowed stereology-based estimates of neuron counts to be obtained in CA1-3 and the dentate gyrus. RESULTS: Morphologic changes were evident in seizure-naive hippocampi of susceptible mice. Dentate granule cell MRI determined that volume was 5% greater in R43Q mice compared with controls (0.628 mm(3), 95% confidence interval [CI] 0.611-0.645 vs 0.595 mm(3), 95% CI 0.571-0.619). The dentate granule cell density was 30% higher in R43Q compared with control mice (553 × 10(3) cells/mm(3), 95% CI 489-616 vs 427 × 10(3) cells/mm(3), 95% CI 362-491). CONCLUSIONS: In a genetic epilepsy model that is both seizure-naive and carries an allele for febrile seizure susceptibility, we have determined hippocampal structural changes that may be applied as a biomarker for seizure susceptibility.
Keywords: Hippocampus
Rights: © 2013 American Academy of Neurology.
RMID: 0030125616
DOI: 10.1212/WNL.0b013e31828970ec
Grant ID: http://purl.org/au-research/grants/nhmrc/436673
http://purl.org/au-research/grants/nhmrc/1005050
http://purl.org/au-research/grants/arc/DP120104112
http://purl.org/au-research/grants/arc/FT0990628
Appears in Collections:Medicine publications

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