Abstract
Transgenic mice overexpressing endothelin-1 (ET-1) in astrocytes (GET-1) displayed more severe brain edema and neurologic dysfunction after experimental ischemic stroke. However, it was not clear whether astrocytic ET-1 contributed to cytotoxic or vasogenic edema associated with stroke. In this study, the role of astrocytic ET-1 in cytotoxic edema and brain injury was investigated. Upon acute water intoxication, the GET-1 mice had a lower survival rate and more severe neurologic deficits. Such an exacerbated condition in the GET-1 mice may be a result of a significant increase in cerebral water content and increased expression of the water channel protein, aquaporin 4 (AQP-4). The GET-1 mice treated with OPC-31260, a nonpeptide arginine vasopressin V2 receptor antagonist, were alleviated from the cerebral water accumulation and neurologic deficit during the early time period after water intoxication. In addition, a significant reduction of AQP-4 expression was observed in astrocytic end-feet AQP-4 in the hippocampus of the GET-1 mice treated with OPC-31260. Therefore, ET-1-induced AQP-4 expression and cerebral water accumulation are the key factors in brain edema associated with acute water intoxication. The V 2 receptor antagonist, OPC-31260, may be one of the effective drugs for the early treatment of ET-1-induced cytotoxic edema and brain injury.
Original language | English (US) |
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Pages (from-to) | 1891-1902 |
Number of pages | 12 |
Journal | Journal of Cerebral Blood Flow and Metabolism |
Volume | 29 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2009 |
Externally published | Yes |
Keywords
- Aquaporin
- Astrocyte
- Cytotoxic edema
- Endothelin-1
- Vasopressin receptor antagonist
- Water intoxication
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
- Cardiology and Cardiovascular Medicine