| Title | Targeted over-expression of endothelin-1 in astrocytes leads to more severe brain damage and vasospasm after subarachnoid hemorrhage |
| Creator | |
| Date Issued | 2013-10-25 |
| Source Publication | BMC Neuroscience
 |
| Volume | 14 |
| Abstract | Background: Endothelin-1 (ET-1) is a potent vasoconstrictor, and astrocytic ET-1 is reported to play a role in the pathogenesis of cerebral ischemic injury and cytotoxic edema. However, it is still unknown whether astrocytic ET-1 also contributes to vasogenic edema and vasospasm during subarachnoid hemorrhage (SAH). In the present study, transgenic mice with astrocytic endothelin-1 over-expression (GET-1 mice) were used to investigate the pathophysiological role of ET-1 in SAH pathogenesis. Results: The GET-1 mice experienced a higher mortality rate and significantly more severe neurological deficits, blood-brain barrier breakdown and vasogenic edema compared to the non-transgenic (Ntg) mice following SAH. Oral administration of vasopressin V receptor antagonist, SR 49059, significantly reduced the cerebral water content in the GET-1 mice. Furthermore, the GET-1 mice showed significantly more pronounced middle cerebral arterial (MCA) constriction after SAH. Immunocytochemical analysis showed that the calcium-activated potassium channels and the phospho-eNOS were significantly downregulated, whereas PKC-α expression was significantly upregulated in the MCA of the GET-1 mice when compared to Ntg mice after SAH. Administration of ABT-627 (ET receptor antagonist) significantly down-regulated PKC-α expression in the MCA of the GET-1 mice following SAH. Conclusions: The present study suggests that astrocytic ET-1 involves in SAH-induced cerebral injury, edema and vasospasm, through ET receptor and PKC-mediated potassium channel dysfunction. Administration of ABT-627 (ET receptor antagonist) and SR 49059 (vasopressin V receptor antagonist) resulted in amelioration of edema and vasospasm in mice following SAH. These data provide a strong rationale to investigate SR 49059 and ABT-627 as therapeutic drugs for the treatment of SAH patients. © 2013 Yeung et al.; licensee BioMed Central Ltd. |
| Keyword | Astrocytes Brain edema Endothelium Subarachnoid hemorrhage Vasospasm |
| DOI | 10.1186/1471-2202-14-131 |
| URL | View source |
| Language | 英语English |
| Scopus ID | 2-s2.0-84886160406 |
| Citation statistics | |
| Document Type | Journal article |
| Identifier | http://repository.uic.edu.cn/handle/39GCC9TT/6532 |
| Collection | Beijing Normal-Hong Kong Baptist University |
| Corresponding Author | Chung，Sookja K. |
| Affiliation | 1.Department of Anatomy,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong SAR,China 2.School of Chinese Medicine,The University of Hong Kong,Hong Kong, SAR,Hong Kong 3.Research Center of Heart,Brain,Hormone and Healthy Aging,The University of Hong Kong,Hong Kong, SAR,Hong Kong 4.Division of Science and Technology,United International College,Zhuhai, Guandong,China 5.Department of Anatomy,The University of Hong Kong,1/F Lab. Block, Faculty of Medicine Bldg., 21 Sassoon Road,Hong Kong, SAR,Hong Kong |
| Recommended Citation GB/T 7714 | Yeung，Patrick K.K.,Shen，Jiangang,Chung，Stephen S.M.et al. Targeted over-expression of endothelin-1 in astrocytes leads to more severe brain damage and vasospasm after subarachnoid hemorrhage[J]. BMC Neuroscience, 2013, 14. |
| APA | Yeung，Patrick K.K., Shen，Jiangang, Chung，Stephen S.M., & Chung，Sookja K. (2013). Targeted over-expression of endothelin-1 in astrocytes leads to more severe brain damage and vasospasm after subarachnoid hemorrhage. BMC Neuroscience, 14. |
| MLA | Yeung，Patrick K.K.,et al."Targeted over-expression of endothelin-1 in astrocytes leads to more severe brain damage and vasospasm after subarachnoid hemorrhage". BMC Neuroscience 14(2013). |
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