Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization

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

Standard

Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization. / Monai, Hiromu; Koketsu, Shinnosuke; Shinohara, Yoshiaki; Ueki, Takatoshi; Kusk, Peter; Hauglund, Natalie L.; Samson, Andrew J.; Nedergaard, Maiken; Hirase, Hajime.

In: Scientific Reports, Vol. 11, No. 1, 8150, 2021.

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

Harvard

Monai, H, Koketsu, S, Shinohara, Y, Ueki, T, Kusk, P, Hauglund, NL, Samson, AJ, Nedergaard, M & Hirase, H 2021, 'Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization', Scientific Reports, vol. 11, no. 1, 8150. https://doi.org/10.1038/s41598-021-87609-w

APA

Monai, H., Koketsu, S., Shinohara, Y., Ueki, T., Kusk, P., Hauglund, N. L., Samson, A. J., Nedergaard, M., & Hirase, H. (2021). Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization. Scientific Reports, 11(1), [8150]. https://doi.org/10.1038/s41598-021-87609-w

Vancouver

Monai H, Koketsu S, Shinohara Y, Ueki T, Kusk P, Hauglund NL et al. Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization. Scientific Reports. 2021;11(1). 8150. https://doi.org/10.1038/s41598-021-87609-w

Author

Monai, Hiromu ; Koketsu, Shinnosuke ; Shinohara, Yoshiaki ; Ueki, Takatoshi ; Kusk, Peter ; Hauglund, Natalie L. ; Samson, Andrew J. ; Nedergaard, Maiken ; Hirase, Hajime. / Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization. In: Scientific Reports. 2021 ; Vol. 11, No. 1.

Bibtex

@article{5c3ecb900d1541f8904a177d40e30f15,
title = "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, 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.",
author = "Hiromu Monai and Shinnosuke Koketsu and Yoshiaki Shinohara and Takatoshi Ueki and Peter Kusk and Hauglund, {Natalie L.} and Samson, {Andrew J.} and Maiken Nedergaard and Hajime Hirase",
year = "2021",
doi = "10.1038/s41598-021-87609-w",
language = "English",
volume = "11",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization

AU - Monai, Hiromu

AU - Koketsu, Shinnosuke

AU - Shinohara, Yoshiaki

AU - Ueki, Takatoshi

AU - Kusk, Peter

AU - Hauglund, Natalie L.

AU - Samson, Andrew J.

AU - Nedergaard, Maiken

AU - Hirase, Hajime

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-021-87609-w

DO - 10.1038/s41598-021-87609-w

M3 - Journal article

C2 - 33854148

AN - SCOPUS:85104304035

VL - 11

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 8150

ER -

ID: 261768794