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Treatment during a vulnerable developmental period rescues a genetic epilepsy

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Treatment during a vulnerable developmental period rescues a genetic epilepsy. / Marguet, Stephan Lawrence; Le-Schulte, Vu Thao Quyen; Merseburg, Andrea; Neu, Axel; Eichler, Ronny; Jakovcevski, Igor; Ivanov, Anton; Hanganu-Opatz, Ileana Livia; Bernard, Christophe; Morellini, Fabio; Isbrandt, Dirk.

In: NAT MED, Vol. 21, No. 12, 12.2015, p. 1436-44.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Marguet, SL, Le-Schulte, VTQ, Merseburg, A, Neu, A, Eichler, R, Jakovcevski, I, Ivanov, A, Hanganu-Opatz, IL, Bernard, C, Morellini, F & Isbrandt, D 2015, 'Treatment during a vulnerable developmental period rescues a genetic epilepsy', NAT MED, vol. 21, no. 12, pp. 1436-44. https://doi.org/10.1038/nm.3987

APA

Marguet, S. L., Le-Schulte, V. T. Q., Merseburg, A., Neu, A., Eichler, R., Jakovcevski, I., Ivanov, A., Hanganu-Opatz, I. L., Bernard, C., Morellini, F., & Isbrandt, D. (2015). Treatment during a vulnerable developmental period rescues a genetic epilepsy. NAT MED, 21(12), 1436-44. https://doi.org/10.1038/nm.3987

Vancouver

Marguet SL, Le-Schulte VTQ, Merseburg A, Neu A, Eichler R, Jakovcevski I et al. Treatment during a vulnerable developmental period rescues a genetic epilepsy. NAT MED. 2015 Dec;21(12):1436-44. https://doi.org/10.1038/nm.3987

Bibtex

@article{1555f2f28c2e46b5a65246ec7d9cf12d,
title = "Treatment during a vulnerable developmental period rescues a genetic epilepsy",
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.",
author = "Marguet, {Stephan Lawrence} and Le-Schulte, {Vu Thao Quyen} and Andrea Merseburg and Axel Neu and Ronny Eichler and Igor Jakovcevski and Anton Ivanov and Hanganu-Opatz, {Ileana Livia} and Christophe Bernard and Fabio Morellini and Dirk Isbrandt",
year = "2015",
month = dec,
doi = "10.1038/nm.3987",
language = "English",
volume = "21",
pages = "1436--44",
journal = "NAT MED",
issn = "1078-8956",
publisher = "NATURE PUBLISHING GROUP",
number = "12",

}

RIS

TY - JOUR

T1 - Treatment during a vulnerable developmental period rescues a genetic epilepsy

AU - Marguet, Stephan Lawrence

AU - Le-Schulte, Vu Thao Quyen

AU - Merseburg, Andrea

AU - Neu, Axel

AU - Eichler, Ronny

AU - Jakovcevski, Igor

AU - Ivanov, Anton

AU - Hanganu-Opatz, Ileana Livia

AU - Bernard, Christophe

AU - Morellini, Fabio

AU - Isbrandt, Dirk

PY - 2015/12

Y1 - 2015/12

N2 - 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.

AB - 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.

U2 - 10.1038/nm.3987

DO - 10.1038/nm.3987

M3 - SCORING: Journal article

C2 - 26594844

VL - 21

SP - 1436

EP - 1444

JO - NAT MED

JF - NAT MED

SN - 1078-8956

IS - 12

ER -