Adrenergic receptor antagonism induces neuroprotection and facilitates recovery from acute ischemic stroke.
Hiromu MonaiXiaowen WangKazuko YahagiNanhong LouHumberto MestreQiwu XuYoichiro AbeMasato YasuiYouichi IwaiMaiken NedergaardHajime HirasePublished in: Proceedings of the National Academy of Sciences of the United States of America (2019)
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.
Keyphrases
- acute ischemic stroke
- cerebral ischemia
- cerebrospinal fluid
- atrial fibrillation
- drug induced
- randomized controlled trial
- adverse drug
- liver failure
- brain injury
- oxidative stress
- diabetic rats
- subarachnoid hemorrhage
- white matter
- binding protein
- respiratory failure
- intensive care unit
- angiotensin converting enzyme
- resting state
- acute coronary syndrome
- functional connectivity
- extracorporeal membrane oxygenation
- acute respiratory distress syndrome
- angiotensin ii
- mechanical ventilation
- loop mediated isothermal amplification
- sensitive detection