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Furosemide prevents membrane KCC2 downregulation during convulsant stimulation in the hippocampus

In adults, γ-aminobutyric acid (GABA) type A receptor (GABA(A)R)-mediated inhibition depends on the maintenance of low intracellular chloride anion concentration through neuron-specific potassium-chloride cotransporter-2 (KCC2). KCC2 has been widely reported to have a plasticity change during the co...

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Autores principales: Chen, Lulan, Yu, Jiangning, Wan, Li, Wu, Zheng, Wang, Guoxiang, Hu, Zihan, Ren, Liang, Zhou, Jing, Qian, Binbin, Zhao, Xuan, Zhang, Jinwei, Liu, Xu, Wang, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210493/
https://www.ncbi.nlm.nih.gov/pubmed/35746976
http://dx.doi.org/10.1016/j.ibneur.2022.04.010
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author Chen, Lulan
Yu, Jiangning
Wan, Li
Wu, Zheng
Wang, Guoxiang
Hu, Zihan
Ren, Liang
Zhou, Jing
Qian, Binbin
Zhao, Xuan
Zhang, Jinwei
Liu, Xu
Wang, Yun
author_facet Chen, Lulan
Yu, Jiangning
Wan, Li
Wu, Zheng
Wang, Guoxiang
Hu, Zihan
Ren, Liang
Zhou, Jing
Qian, Binbin
Zhao, Xuan
Zhang, Jinwei
Liu, Xu
Wang, Yun
author_sort Chen, Lulan
collection PubMed
description In adults, γ-aminobutyric acid (GABA) type A receptor (GABA(A)R)-mediated inhibition depends on the maintenance of low intracellular chloride anion concentration through neuron-specific potassium-chloride cotransporter-2 (KCC2). KCC2 has been widely reported to have a plasticity change during the course of epilepsy development, with an early downregulation and late recovery in neuronal cell membranes after epileptic stimulation, which facilitates epileptiform burst activity. Furosemide is a clinical loop diuretic that inhibits KCC2. Here, we first confirmed that furosemide pretreatment could effectively prevented convulsant stimulation-induced neuronal membrane KCC2 downregulation in the hippocampus in both in vivo and in vitro cyclothiazide-induced seizure model. Second, we verified that furosemide pretreatment rescued KCC2 function deficits, as indicated by E(GABA) depolarizing shift and GABA(A)R inhibitory function impairment induced via cyclothiazide treatment. Further, we demonstrated that furosemide also suppressed cyclothiazide-induced epileptiform burst activity in cultured hippocampal neurons and lowered the mortality rate during acute seizure induction. Overall, furosemide prevents membrane KCC2 downregulation during acute seizure induction, restores KCC2-mediated GABA inhibition, and interrupts the progression from acute seizure to epileptogenesis.
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spelling pubmed-92104932022-06-22 Furosemide prevents membrane KCC2 downregulation during convulsant stimulation in the hippocampus Chen, Lulan Yu, Jiangning Wan, Li Wu, Zheng Wang, Guoxiang Hu, Zihan Ren, Liang Zhou, Jing Qian, Binbin Zhao, Xuan Zhang, Jinwei Liu, Xu Wang, Yun IBRO Neurosci Rep Articles from the Specail Issue Neural plasticity In adults, γ-aminobutyric acid (GABA) type A receptor (GABA(A)R)-mediated inhibition depends on the maintenance of low intracellular chloride anion concentration through neuron-specific potassium-chloride cotransporter-2 (KCC2). KCC2 has been widely reported to have a plasticity change during the course of epilepsy development, with an early downregulation and late recovery in neuronal cell membranes after epileptic stimulation, which facilitates epileptiform burst activity. Furosemide is a clinical loop diuretic that inhibits KCC2. Here, we first confirmed that furosemide pretreatment could effectively prevented convulsant stimulation-induced neuronal membrane KCC2 downregulation in the hippocampus in both in vivo and in vitro cyclothiazide-induced seizure model. Second, we verified that furosemide pretreatment rescued KCC2 function deficits, as indicated by E(GABA) depolarizing shift and GABA(A)R inhibitory function impairment induced via cyclothiazide treatment. Further, we demonstrated that furosemide also suppressed cyclothiazide-induced epileptiform burst activity in cultured hippocampal neurons and lowered the mortality rate during acute seizure induction. Overall, furosemide prevents membrane KCC2 downregulation during acute seizure induction, restores KCC2-mediated GABA inhibition, and interrupts the progression from acute seizure to epileptogenesis. Elsevier 2022-04-28 /pmc/articles/PMC9210493/ /pubmed/35746976 http://dx.doi.org/10.1016/j.ibneur.2022.04.010 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles from the Specail Issue Neural plasticity
Chen, Lulan
Yu, Jiangning
Wan, Li
Wu, Zheng
Wang, Guoxiang
Hu, Zihan
Ren, Liang
Zhou, Jing
Qian, Binbin
Zhao, Xuan
Zhang, Jinwei
Liu, Xu
Wang, Yun
Furosemide prevents membrane KCC2 downregulation during convulsant stimulation in the hippocampus
title Furosemide prevents membrane KCC2 downregulation during convulsant stimulation in the hippocampus
title_full Furosemide prevents membrane KCC2 downregulation during convulsant stimulation in the hippocampus
title_fullStr Furosemide prevents membrane KCC2 downregulation during convulsant stimulation in the hippocampus
title_full_unstemmed Furosemide prevents membrane KCC2 downregulation during convulsant stimulation in the hippocampus
title_short Furosemide prevents membrane KCC2 downregulation during convulsant stimulation in the hippocampus
title_sort furosemide prevents membrane kcc2 downregulation during convulsant stimulation in the hippocampus
topic Articles from the Specail Issue Neural plasticity
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210493/
https://www.ncbi.nlm.nih.gov/pubmed/35746976
http://dx.doi.org/10.1016/j.ibneur.2022.04.010
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