RRC ID 57615
Author Monai H, Wang X, Yahagi K, Lou N, Mestre H, Xu Q, Abe Y, Yasui M, Iwai Y, Nedergaard M, Hirase H.
Title Adrenergic receptor antagonism induces neuroprotection and facilitates recovery from acute ischemic stroke.
Journal Proc Natl Acad Sci U S A
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.
Volume 116(22)
Pages 11010-11019
Published 2019-5-28
DOI 10.1073/pnas.1817347116
PII 1817347116
PMID 31097598
PMC PMC6561179
MeSH Adrenergic Antagonists / pharmacology* Animals Aquaporin 4 / metabolism Astrocytes / metabolism Brain Ischemia / metabolism* Disease Models, Animal Female Male Mice Mice, Inbred C57BL Neuroprotection / drug effects* Potassium / metabolism Stroke / metabolism*
IF 9.58
Times Cited 5
Mice RBRC09650