Marguet, Stephan Lawrence, Le-Schulte, Vu Thao Quyen, Merseburg, Andrea, Neu, Axel ORCID: 0000-0001-7045-7194, Eichler, Ronny, Jakovcevski, Igor ORCID: 0000-0001-7673-9600, Ivanov, Anton ORCID: 0000-0002-8650-6322, Hanganu-Opatz, Ileana Livia, Bernard, Christophe, Morellini, Fabio and Isbrandt, Dirk (2015). Treatment during a vulnerable developmental period rescues a genetic epilepsy. Nat. Med., 21 (12). S. 1436 - 1448. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-170X
Full text not available from this repository.Abstract
The nervous system is vulnerable to perturbations during specific developmental periods. Insults during such susceptible time windows can have long-term consequences, including the development of neurological diseases such as epilepsy. Here we report that a pharmacological intervention timed during a vulnerable neonatal period of cortical development prevents pathology in a genetic epilepsy model. By using mice with dysfunctional Kv7 voltage-gated K+ channels, which are mutated in human neonatal epilepsy syndromes, we demonstrate the safety and efficacy of the sodium-potassium-chloride cotransporter NKCC1 antagonist bumetanide, which was administered during the first two postnatal weeks. In Kv7 current-deficient mice, which normally display epilepsy, hyperactivity and stereotypies as adults, transient bumetanide treatment normalized neonatal in vivo cortical network and hippocampal neuronal activity, prevented structural damage in the hippocampus and restored wild-type adult behavioral phenotypes. Furthermore, bumetanide treatment did not adversely affect control mice. These results suggest that in individuals with disease susceptibility, timing prophylactically safe interventions to specific windows during development may prevent or arrest disease progression.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-385424 | ||||||||||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1038/nm.3987 | ||||||||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Nat. Med. | ||||||||||||||||||||||||||||||||||||||||||||||||
Volume: | 21 | ||||||||||||||||||||||||||||||||||||||||||||||||
Number: | 12 | ||||||||||||||||||||||||||||||||||||||||||||||||
Page Range: | S. 1436 - 1448 | ||||||||||||||||||||||||||||||||||||||||||||||||
Date: | 2015 | ||||||||||||||||||||||||||||||||||||||||||||||||
Publisher: | NATURE PUBLISHING GROUP | ||||||||||||||||||||||||||||||||||||||||||||||||
Place of Publication: | NEW YORK | ||||||||||||||||||||||||||||||||||||||||||||||||
ISSN: | 1546-170X | ||||||||||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/38542 |
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