Adrenergic receptor antagonism induces neuroprotection and facilitates recovery from acute ischemic stroke

Hiromu Monai; Xiaowen Wang; Kazuko Yahagi; Nanhong Lou; Humberto Mestre; Qiwu Xu; Yoichiro Abe; Masato Yasui; Youichi Iwai; Maiken Nedergaard; Hajime Hirase

doi:10.1073/pnas.1817347116

Adrenergic receptor antagonism induces neuroprotection and facilitates recovery from acute ischemic stroke

Hiromu Monai, Xiaowen Wang, Kazuko Yahagi, Nanhong Lou, Humberto Mestre, Qiwu Xu, Yoichiro Abe, Masato Yasui, Youichi Iwai, Maiken Nedergaard, Hajime Hirase

Department of Pharmacology

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Spontaneous waves of cortical spreading depolarization (CSD) are induced in the setting of acute focal ischemia. CSD is linked to a sharp increase of extracellular K⁺ that induces a long-lasting suppression of neural activity. Furthermore, CSD induces secondary irreversible damage in the ischemic brain, suggesting that K⁺ homeostasis might constitute a therapeutic strategy in ischemic stroke. Here we report that adrenergic receptor (AdR) antagonism accelerates normalization of extracellular K⁺, resulting in faster recovery of neural activity after photothrombotic stroke. Remarkably, systemic adrenergic blockade before or after stroke facilitated functional motor recovery and reduced infarct volume, paralleling the preservation of the water channel aquaporin-4 in astrocytes. Our observations suggest that AdR blockers promote cerebrospinal fluid exchange and rapid extracellular K⁺ clearance, representing a potent potential intervention for acute stroke.

Original language	English
Pages (from-to)	11010-11019
Number of pages	10
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	166
Issue number	22
DOIs	https://doi.org/10.1073/pnas.1817347116
Publication status	Published - 2019 May 28

Keywords

AQP4
Adrenergic receptor
Aquaporin-4
Extracellular potassium
Ion
Photothrombotic stroke

ASJC Scopus subject areas

General

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10.1073/pnas.1817347116

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Monai, H., Wang, X., Yahagi, K., Lou, N., Mestre, H., Xu, Q., Abe, Y., Yasui, M., Iwai, Y., Nedergaard, M., & Hirase, H. (2019). Adrenergic receptor antagonism induces neuroprotection and facilitates recovery from acute ischemic stroke. Proceedings of the National Academy of Sciences of the United States of America, 166(22), 11010-11019. https://doi.org/10.1073/pnas.1817347116

Adrenergic receptor antagonism induces neuroprotection and facilitates recovery from acute ischemic stroke. / Monai, Hiromu; Wang, Xiaowen; Yahagi, Kazuko; Lou, Nanhong; Mestre, Humberto; Xu, Qiwu; Abe, Yoichiro ; Yasui, Masato; Iwai, Youichi; Nedergaard, Maiken; Hirase, Hajime.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 166, No. 22, 28.05.2019, p. 11010-11019.

Research output: Contribution to journal › Article › peer-review

Monai, H, Wang, X, Yahagi, K, Lou, N, Mestre, H, Xu, Q, Abe, Y , Yasui, M, Iwai, Y, Nedergaard, M & Hirase, H 2019, 'Adrenergic receptor antagonism induces neuroprotection and facilitates recovery from acute ischemic stroke', Proceedings of the National Academy of Sciences of the United States of America, vol. 166, no. 22, pp. 11010-11019. https://doi.org/10.1073/pnas.1817347116

Monai, Hiromu ; Wang, Xiaowen ; Yahagi, Kazuko ; Lou, Nanhong ; Mestre, Humberto ; Xu, Qiwu ; Abe, Yoichiro ; Yasui, Masato ; Iwai, Youichi ; Nedergaard, Maiken ; Hirase, Hajime. / Adrenergic receptor antagonism induces neuroprotection and facilitates recovery from acute ischemic stroke. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 166, No. 22. pp. 11010-11019.

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abstract = "Spontaneous waves of cortical spreading depolarization (CSD) are induced in the setting of acute focal ischemia. CSD is linked to a sharp increase of extracellular K+ that induces a long-lasting suppression of neural activity. Furthermore, CSD induces secondary irreversible damage in the ischemic brain, suggesting that K+ homeostasis might constitute a therapeutic strategy in ischemic stroke. Here we report that adrenergic receptor (AdR) antagonism accelerates normalization of extracellular K+, resulting in faster recovery of neural activity after photothrombotic stroke. Remarkably, systemic adrenergic blockade before or after stroke facilitated functional motor recovery and reduced infarct volume, paralleling the preservation of the water channel aquaporin-4 in astrocytes. Our observations suggest that AdR blockers promote cerebrospinal fluid exchange and rapid extracellular K+ clearance, representing a potent potential intervention for acute stroke.",

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AU - Xu, Qiwu

AU - Abe, Yoichiro

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