Neuroprotective Effect of Buyang Huanwu Decoction on Rat Ischemic/Reperfusion Brain Damage by Promoting Migration of Neural Precursor Cells

Buyang Huanwu Decoction (BYHWD) is a classic formula widely used for treating stroke-induced disability, the highest morbidity of neurological disorders in China. However, the mechanism of its neuroprotection has not been fully clarified. Previous reports indicated that BYHWD may promote growth and differentiation of neural precursor cells (NPCs). The present study focused on the effects of BYHWD on migration of NPCs in rats with middle cerebral artery occlusion (MCAO). Rats were treated with different doses of BYHWD (12 and 24 grams/kg) from day 1 to day 21 after model building. BYHWD could increase the survival rate and decrease neurological scores and infarct volume as compared with the vehicle-treated MCAO rats. Moreover, BYHWD treatment significantly increased 5-bromo-2-deoxyuridine (BrdU)-positive cells in the subventricular zone (SVZ), sub-granular zone (SGZ), and corpus striatum (CS) of the infarct brain. Interestingly, BYHWD could markedly enhance BrdU(+)/doublecortin(+) cells not only in the SVZ and SGZ but also in CS, by up-regulating the protein expression of migration activators, including stromal cell derived factor-1, CXC chemokine receptor 4, vascular endothelial growth factor, Reelin, and brain-derived neurotrophic factor in the ipsilateral infarct area after MCAO. In addition, BYHWD treatment was able to promote the neuronal differentiation, which was closely related to the migratory process of NPCs in MCAO rats. These findings offer evidence for the first time that BYHWD may exert its neuroprotective effects partially by promotion of NPCs migration to ischemic brain areas.