Effects of donepezil on the expression of neurotrophic related factors in subventricular zone of cerebral infarction mice

Objective To investigate the effect of donepezil on subventricular zone (SVZ) neurogenesis related neurotrophic factors after cerebral infarction. Methods Mice were randomly assigned into three groups: vehicle-treated sham group (Sham+ vehicle, n=18), vehicle-treated middle cerebral artery occlusion (MCAO) group (MCAO + vehicle, n=30) and donepezil-treated MCAO group (MCAO+ donepezil, n=30). Middle cerebral artery occlusion(MCAO) was induced by thread-occlusion method. Nissl staining was used to measure the infarct volume and the modified neurological severity score(mNSS) was used to assess neurologic function and brain water content was detected to assess brain edema degree. Proliferative cells and neuroblasts were labeled with 5-bromodeoxyuridine (BrdU) and doublecortin (DCX). The SVZ BrdU+ /DCX+ cells were detected by immunofluorescence.The expression of glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were detected by Western blot. Results The infarct volume of MCAO + donepezil group ((13.33±4.55)%) was significantly lower than that of MCAO + vehicle group ((31.33±3.93)%, t=7.34, P<0.05). The neurologic deficits were significantly ameliorated after donepezil treatment, and the brain water content of MCAO + donepezil group ((71.82±10.18)%)was significantly less than that of MCAO + vehicle group ((85.93±7.54)%, F=13.480, P<0.05). All differences were statistically significant (P<0.05). The area of BrdU+ /DCX+ cells within SVZ of MCAO + vehicle group ((6.16±1.79)%) was significantly larger than that of sham + vehicle group ((2.25±1.09)%), and was fewer than that of MCAO+ donepezil group ((16.19±2.16)%, F=102.756, P<0.05). MCAO significantly promoted the expression of GDNF, BDNF and NGF within SVZ compared with sham operation, and donepezil increased these protein levels(F=15.114, 27.121, 27.398, P<0.05). Conclusion Donepezil regulates neurogenesis via increasesing the expression of GDNF, BDNF and NGF within SVZ after cerebral infarction. Key words: Donepezil; Cerebral infarction; Subventricular zone; Neurogenesis; Neurotrophic factors