Abstract
Subarachnoid hemorrhage (SAH) is a devastating stroke subtype accounting for approximately 3 to 7% of cases each year. Despite its rarity among the various stroke types, SAH is still responsible for approximately 25% of all stroke fatalities. Although various preventative and therapeutic interventions have been explored for potential neuroprotection after SAH, a considerable percentage of patients still experience serious neurologic and/or cognitive impairments as a result of the primary hemorrhage and/or secondary brain damage that occurs. Z-ligustilide (LIG), the primary lipophilic component of the Chinese traditional medicine Radix Angelica sinensis, has been shown to reduce ischemic brain injury via antiapoptotic pathways. Accordingly, in our study, we investigated the neuroprotective potential of LIG after experimental SAH in rats. Rats with SAH that was induced using the established double hemorrhage model were studied with and without LIG treatment. Mortality, neurobehavioral evaluation, brain water content, blood-brain barrier (BBB) permeability, and vasospasm assessment of the basilar artery were measured on days 3 and 7 after injury. Additional testing was done to evaluate for apoptosis using TdT-mediated dUTP-biotin nick end labeling staining as well as immunohistochemistry and Western blotting to identify key proapoptotic/survival proteins, i.e., p53, Bax, Bcl-2, and cleaved caspase-3. The results showed that LIG treatment reduced mortality, neurobehavioral deficits, brain edema, BBB permeability, and cerebral vasospasm. In addition, treatment reduced the number of apoptotic cells in the surrounding brain injury site, which accompanied a marked down-regulation of proapoptotic proteins, p53, and cleaved caspase-3. Our data suggest that LIG may be an effective therapeutic modality for SAH victims by altering apoptotic mechanisms.
Footnotes
This work was supported by the National Basic Research Program of China [Grant 2009CB918300].
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.110.177055.
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ABBREVIATIONS:
- SAH
- subarachnoid hemorrhage
- ANOVA
- analysis of variance
- BA
- basilar artery
- BBB
- blood-brain barrier
- CVS
- cerebral vasospasm
- EB
- Evans blue
- LIG
- Z-ligustilide
- PBS
- phosphate buffer solution
- SD
- Sprague-Dawley
- SNK
- Student-Newman-Keuls
- TUNEL
- TdT-mediated dUTP-biotin nick end labeling
- ROS
- reactive oxygen species.
- Received November 19, 2010.
- Accepted March 9, 2011.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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