Effect of Ginkgo Biloba Extract on Learning and Memory of Developing Rats with Kindled Seizure by Pentetrazole and Proliferation and Differentiation of Hippocampal Neural Stem Cells

Objective To study the effect of Ginkgo biloba extract(EGb) on kindling rats at developmental phase and its relationship with learning and memory. Methods Postnatal 21 days(P21) Sprague-Dawley(SD) rats were grouped randomly into 5 groups including normal sodium controls(NS group),pentylenetetrazol(PTZ)kindling models(P7 group and P14 group,PTZ 35 mg·kg-1·d-1,ip) and EGb groups(EGb 7 d group and EGb 14 d group,EGb 300 mg·kg-1·d-1,po),which all rats was preliminary screened by Y-maze test.Then hippocampal neural stem cells(NSCs) proliferation of CA1 and CA3 granular cell layer was studied by immunohistochemical method for all experimental rats,which Nestin positive cells were regarded as marker of NSCs.Meanwhile,5-bromo-deoxy-uridine(BrdU) served as the marker of cell proliferation,NeuN which was a marker of neuron,GFAP which was a marker of astrocytes were observed for differentiation of proliferative NSCs. Results 1.Compared with the NS group,the times of every kindled group rats reaching academic standard were increased significantly by Y-maze test(P0.01).The number of reaching the learning standards of rats after treatment of EGb for 7 days and 14 days were significantly less than that in PTZ kindling group(Pa0.01).2.For NSCs proliferation,Nestin positive cells under or within granular cell layer of CA1 or CA3 in hippocampus of PTZ kindled rats increased significantly compared with NS group(P0.01),meanwhile,that in EGb 7 d and EGb 14 d groups were more than that of corresponding PTZ kindled rats(P0.05).The Nestin positive cell of CA1 and CA3 region of rats with EGb 7 d and EGb 14 d were compared and found that Nestin positive cells in EGb 14 d rats were less those that in EGb 7 d rats for NSCs differentiation(P0.05).3.The number of BrdU/NeuN cells in PTZ kindled group was less than that in EGb treatment groups.The percentage of BrdU/NeuN positive cells in hippocampus in EGb 14 d group was higher than that in EGb 7 d group(Pa0.05).Meanwhile,4%-5% co-expression of GFAP with BrdU was found after EGb treatment. Conclusions EGb can significantly improve the learning and memory function of kindled rats.The possible mechanism of EGb treatment for improving learning-memory dysfunction may be related to influence the NSCs proliferation and differentiation of hippocampus in kindled rats.