A combination of NMDA and AMPA receptor antagonists retards granule cell dispersion and epileptogenesis in a model of acquired epilepsy View Full Text


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Article Info

DATE

2017-09-22

AUTHORS

Alina Schidlitzki, Friederike Twele, Rebecca Klee, Inken Waltl, Kerstin Römermann, Sonja Bröer, Sebastian Meller, Ingo Gerhauser, Vladan Rankovic, Dandan Li, Claudia Brandt, Marion Bankstahl, Kathrin Töllner, Wolfgang Löscher

ABSTRACT

Epilepsy may arise following acute brain insults, but no treatments exist that prevent epilepsy in patients at risk. Here we examined whether a combination of two glutamate receptor antagonists, NBQX and ifenprodil, acting at different receptor subtypes, exerts antiepileptogenic effects in the intrahippocampal kainate mouse model of epilepsy. These drugs were administered over 5 days following kainate. Spontaneous seizures were recorded by video/EEG at different intervals up to 3 months. Initial trials showed that drug treatment during the latent period led to higher mortality than treatment after onset of epilepsy, and further, that combined therapy with both drugs caused higher mortality at doses that appear safe when used singly. We therefore refined the combined-drug protocol, using lower doses. Two weeks after kainate, significantly less mice of the NBQX/ifenprodil group exhibited electroclinical seizures compared to vehicle controls, but this effect was lost at subsequent weeks. The disease modifying effect of the treatment was associated with a transient prevention of granule cell dispersion and less neuronal degeneration in the dentate hilus. These data substantiate the involvement of altered glutamatergic transmission in the early phase of epileptogenesis. Longer treatment with NBQX and ifenprodil may shed further light on the apparent temporal relationship between dentate gyrus reorganization and development of spontaneous seizures. More... »

PAGES

12191

References to SciGraph publications

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  • Identifiers

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    http://scigraph.springernature.com/pub.10.1038/s41598-017-12368-6

    DOI

    http://dx.doi.org/10.1038/s41598-017-12368-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1091849496

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28939854


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    368 grid-institutes:grid.412970.9 schema:alternateName Center for Systems Neuroscience, 30559 Hannover, Germany
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    377 Present Address: Institute for Auditory Neuroscience at University Medical Center Göttingen & German Primate Center, Göttingen, Germany
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