Ischemic stroke remains a serious threat to human life. There are limited effective
therapies for the treatment of
stroke. We have previously demonstrated that angiogenesis and neurogenesis in the brain play an important role in functional recovery following
ischemic stroke. Recent studies indicate that increased arteriogenesis and collateral circulation are determining factors for restoring reperfusion and outcomes of
stroke patients.
Danshensu, the
Salvia miltiorrhiza root extract, is used in treatments of various human ischemic events in
traditional Chinese medicine. Its therapeutic mechanism, however, is not well clarified. Due to its proposed effect on angiogenesis and arteriogenesis, we hypothesized that
danshensu could benefit
stroke recovery through stimulating neurogenesis and collaterogenesis in the post-
ischemia brain. Focal
ischemic stroke targeting the right sensorimotor cortex was induced in wild-type C57BL6 mice and transgenic mice expressing
green fluorescent protein (GFP) to label smooth muscle cells of brain arteries.
Sodium danshensu (SDS, 700 mg/kg) was administered intraperitoneally (i.p.) 10 min after
stroke and once daily until animals were sacrificed. To label proliferating cells,
5-bromo-2'-deoxyuridine (
BrdU; 50 mg/kg, i.p.) was administered, starting on day 3 after
ischemia and continued once daily until sacrifice. At 14 days after
stroke, SDS significantly increased the expression of
vascular endothelial growth factor (
VEGF), stromal-derived factor-1 (SDF-1),
brain-derived neurotrophic factor (
BDNF), and
endothelial nitric oxide synthase (eNOS) in the peri-
infarct region. SDS-treated animals showed increased number of doublecortin (DCX)-positive cells. Greater numbers of proliferating endothelial cells and smooth muscle cells were detected in SDS-treated mice 21 days after
stroke in comparison with vehicle controls. The number of newly formed neurons labeled by NeuN and
BrdU antibodies increased in SDS-treated mice 28 days after
stroke. SDS significantly increased the newly formed arteries and the diameter of collateral arteries, leading to enhanced local cerebral blood flow recovery after
stroke. These results suggest that systemic
sodium danshensu treatment shows significant regenerative effects in the post-ischemic brain, which may benefit long-term functional recovery from
ischemic stroke.