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.