Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
I: Scientific Reports, Bind 11, Nr. 1, 8150, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
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