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

研究成果: Article査読

16 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)11010-11019
ページ数10
ジャーナルProceedings of the National Academy of Sciences of the United States of America
166
22
DOI
出版ステータスPublished - 2019 5月 28

ASJC Scopus subject areas

  • 一般

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