Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 22, Pages 11010-11019Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1817347116
Keywords
photothrombotic stroke; adrenergic receptor; extracellular potassium ion; aquaporin-4; AQP4
Categories
Funding
- RIKEN Center for Brain Science
- Japan Society for the Promotion of Science KAKENHI [18K14859, 26117520, 16H01888, 18H05150, 17K19637, 16H05134, 15H04688, 18H02606]
- Human Frontier Science Program Grant [RGP0036/2014]
- Japan Society for the Promotion of Science Core-to-Core Program Advanced Research Networks
- Adelson Medical Research Foundation
- Lundbeck Foundation
- Novo Nordisk Foundation
- US Department of Defense
- Grants-in-Aid for Scientific Research [16H05134, 17K19637, 18H05150, 18H02606, 18K14859, 15H04688] Funding Source: KAKEN
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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 Ion 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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