Objective: To investigate the effect and possible mechanism of Qixian Tongluo decoction on endogenous neural stem cells regeneration after cerebral ischemia in rats. Method: The focal cerebral ischemia model was established by the method of middle cerebral artery occlusion (MCAO). A total of 160 rats were randomly divided into normal group

sham operation group

model group

piracetam group (piracetam tablets intragastric administration)

and Qixian Tongluo decoction group (Qixian Tongluo decoction intragastric administration). 5-Bromodeoxyuridine (BrdU) was injected intraperitoneally to label proliferating cells in brain; at day 3

7

14 and 28 after MCAO modeling

the neonatal neurons and astrocytes in the ischemic hippocampus were detected by immunofluorescence BrdU/neuron nuclear antigen (NeuN) and BrdU/glial fibrillary acidic protein (GFAP) double staining

and then the positive rate of double labeling cells was calculated. In addition

the expression level of brain derived neurotrophic factor (BDNF) in the ischemic brain was detected by immunohistochemistry. Result: The percentages of BrdU/NeuN and BrdU/GFAP double-labeled positive cells in Qixian Tongluo decoction group and piracetam group were all higher than those in the model group at day 7

14 and 28 after cerebral ischemia (P<0.01). The percentages of BrdU/NeuN positive cells in Qixian Tongluo decoction group were all higher than those in piracetam group at different time points (P<0.05); however

the percentage of BrdU/GFAP double-labeled positive cells in Qixian Tongluo decoction group was higher than that of piracetam group only at day 7 after MCAO (P<0.05)

and then the percentages were decreased in both groups. As compared with the model group

the expression levels of BDNF in the ischemic brain of Qixian Tongluo decoction group and piracetam group were all higher at different time points after cerebral ischemia (P<0.01). The expression level of BDNF in Qixian Tongluo decoction group reached the peak at day 3 after MCAO

and then declined at the following time points

but still higher than that in the piracetam group (P<0.05). Conclusion: Qixian Tongluo decoction can promote endogenous neural stem cells regeneration in rats with cerebral ischemia especially during convalescence and sequelae stages

and the early activation of astrocytes and upregulation of BDNF in ischemia brain may be one of its mechanisms.