Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization

Abstract Cortical spreading depolarization (CSD) is a propagating wave of tissue depolarization characterized by a large increase of extracellular potassium concentration and prolonged subsequent electrical silencing of neurons. Waves of CSD arise spontaneously in various acute neurological settings...

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Autores principales:	Hiromu Monai, Shinnosuke Koketsu, Yoshiaki Shinohara, Takatoshi Ueki, Peter Kusk, Natalie L. Hauglund, Andrew J. Samson, Maiken Nedergaard, Hajime Hirase
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c8a2b7c39e79416a9df5bd64aefd4976
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spelling	oai:doaj.org-article:c8a2b7c39e79416a9df5bd64aefd49762021-12-02T15:51:12ZAdrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization10.1038/s41598-021-87609-w2045-2322https://doaj.org/article/c8a2b7c39e79416a9df5bd64aefd49762021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87609-whttps://doaj.org/toc/2045-2322Abstract Cortical spreading depolarization (CSD) is a propagating wave of tissue depolarization characterized by a large increase of extracellular potassium concentration and prolonged subsequent electrical silencing of neurons. Waves of CSD arise spontaneously in various acute neurological settings, including migraine aura and ischemic stroke. Recently, we have reported that pan-inhibition of adrenergic receptors (AdRs) facilitates the normalization of extracellular potassium after acute photothrombotic stroke in mice. Here, we have extended that mechanistic study to ask whether AdR antagonists also modify the dynamics of KCl-induced CSD and post-CSD recovery in vivo. Spontaneous neural activity and KCl-induced CSD were visualized by cortex-wide transcranial Ca2+ imaging in G-CaMP7 transgenic mice. AdR antagonism decreased the recurrence of CSD waves and accelerated the post-CSD recovery of neural activity. Two-photon imaging revealed that astrocytes exhibited aberrant Ca2+ signaling after passage of the CSD wave. This astrocytic Ca2+ activity was diminished by the AdR antagonists. Furthermore, AdR pan-antagonism facilitated the normalization of the extracellular potassium level after CSD, which paralleled the recovery of neural activity. These observations add support to the proposal that neuroprotective effects of AdR pan-antagonism arise from accelerated normalization of extracellular K+ levels in the setting of acute brain injury.Hiromu MonaiShinnosuke KoketsuYoshiaki ShinoharaTakatoshi UekiPeter KuskNatalie L. HauglundAndrew J. SamsonMaiken NedergaardHajime HiraseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiromu Monai Shinnosuke Koketsu Yoshiaki Shinohara Takatoshi Ueki Peter Kusk Natalie L. Hauglund Andrew J. Samson Maiken Nedergaard Hajime Hirase Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization
description	Abstract Cortical spreading depolarization (CSD) is a propagating wave of tissue depolarization characterized by a large increase of extracellular potassium concentration and prolonged subsequent electrical silencing of neurons. Waves of CSD arise spontaneously in various acute neurological settings, including migraine aura and ischemic stroke. Recently, we have reported that pan-inhibition of adrenergic receptors (AdRs) facilitates the normalization of extracellular potassium after acute photothrombotic stroke in mice. Here, we have extended that mechanistic study to ask whether AdR antagonists also modify the dynamics of KCl-induced CSD and post-CSD recovery in vivo. Spontaneous neural activity and KCl-induced CSD were visualized by cortex-wide transcranial Ca2+ imaging in G-CaMP7 transgenic mice. AdR antagonism decreased the recurrence of CSD waves and accelerated the post-CSD recovery of neural activity. Two-photon imaging revealed that astrocytes exhibited aberrant Ca2+ signaling after passage of the CSD wave. This astrocytic Ca2+ activity was diminished by the AdR antagonists. Furthermore, AdR pan-antagonism facilitated the normalization of the extracellular potassium level after CSD, which paralleled the recovery of neural activity. These observations add support to the proposal that neuroprotective effects of AdR pan-antagonism arise from accelerated normalization of extracellular K+ levels in the setting of acute brain injury.
format	article
author	Hiromu Monai Shinnosuke Koketsu Yoshiaki Shinohara Takatoshi Ueki Peter Kusk Natalie L. Hauglund Andrew J. Samson Maiken Nedergaard Hajime Hirase
author_facet	Hiromu Monai Shinnosuke Koketsu Yoshiaki Shinohara Takatoshi Ueki Peter Kusk Natalie L. Hauglund Andrew J. Samson Maiken Nedergaard Hajime Hirase
author_sort	Hiromu Monai
title	Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization
title_short	Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization
title_full	Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization
title_fullStr	Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization
title_full_unstemmed	Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization
title_sort	adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c8a2b7c39e79416a9df5bd64aefd4976
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Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization

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