| 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
|
| Resource |
| Mice |
RBRC09650 |
