OBJECTIVETo explore the effect of Buyang Huanwu Decoction (BYHWD) and its disassembled recipes on rats' neurogenesis after focal cerebral ischemia and to investigate its underlying molecular mechanisms.

METHODSFocal cerebral ischemia model was induced by occlusion of the right middle cerebral artery for 90 min using the intraluminal filament model. Rats were divided into the sham-operation group, the model group, the BYHWD group, the qi supplementing group, and the blood activating group. Medication was performed by gastrogavage 24 h after ischemia for 14 successive days. 5-bromodeoxyuridine (BrdU) (at 50 mg/kg) was intraperitoneally injected, once per day for 14 successive days. The neurological function was assessed using modified neurological severity score (mNSS) and the corner test at day 1, 7, and 14 after ischemia. BrdU/Nestin, BrdU/NeuN, and BrdU/GFAP positive cells were examined by double immunofluorescence at day 14 after ischemia. The protein expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were detected by Western blot at day 14 after ischemia.

RESULTSCompared with the model group, the score of mNSS and the frequency of turning right significantly decreased in the BYHWD group and the qi supplementing group (P < 0.01), the number of BrdU/Nestin in the subventricular zone of the lateral ventricle, and BrdU/ NeuN and BrdU/GFAP positive cells in the peripheral ischemic cortex increased (P < 0.05, P < 0.01), protein expression of BDNF and VEGF increased (P < 0.05, P < 0.01). In the qi supplementing group, there was no statistical difference in BrdU/GFAP. But there was no statistical difference in each index of the blood activating group (P > 0.05). Compared with BYHWD group, the number of BrdU/Nestin, BrdU/ NeuN, and BrdU/GFAP positive cells significantly decreased (P < 0.01), and the protein expression of BDNF and VEGF were significantly reduced in the qi supplementing group and the blood activating group (P < 0.01).

CONCLUSIONSBYHWD could significantly improve neurogenesis and neurological function recovery after focal cerebral ischemia in rats. Its mechanisms might be related to up-regulating protein expression of BDNF and VEGF. Drugs for qi supplementing and drugs for blood activating had synergistic effects.

Animals ; Brain Ischemia ; drug therapy ; metabolism ; Brain-Derived Neurotrophic Factor ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Neurogenesis ; drug effects ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; metabolism