Targeted overexpression of endothelin-1 in astrocytes leads to more severe cytotoxic brain edema and higher mortality

Patrick Ka Kit Yeung, Amy Cheuk Yin Lo, Justin Wai Chung Leung, Stephen Sum Man Chung, Sookja Kim Chung

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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 languageEnglish (US)
Pages (from-to)1891-1902
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number12
StatePublished - Dec 2009
Externally publishedYes


  • Aquaporin
  • Astrocyte
  • Cytotoxic edema
  • Endothelin-1
  • Vasopressin receptor antagonist
  • Water intoxication

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Targeted overexpression of endothelin-1 in astrocytes leads to more severe cytotoxic brain edema and higher mortality'. Together they form a unique fingerprint.

Cite this