| Neural stem cells exist in the subventricular zone (SVZ) of lateral ventricle and the dentate gyrus (DG) of hippocampus in central neural system (CNS) throughout the life of adult mammals, so does neurogenesis in adult brain. Neurogenesis is regulated by many factors including aging, chronic stress, depression, growth factors and brain injury, et al, in which the most important is growth factors. The stages of neurogenesis can be divided into three steps: proliferation .. migration and differentiation. Insulin-like growth factor-1 (IGF-1) is a polypetide hormone that has demonstrated effects on these neural progenitor cells. IGF-1 concentration in brain and serum shows a significant correlation with age. In the present studies, Experiment I is for elucidating detail relationship between proliferation, migration and differentiation of NSCs in adult brain after focal ischemia and IGF-1 focal application; Experiment II is for illustrating the difference of neurogenesis and the influences of IGF-1 (by intracerebroventricular infusing) on neurogenesis and the survival of proliferated cells in young and older rats.Materials and Method:Experiment 1: Health male SD rats were divided into MCAO-treated group (n=16), MCAO-control group (n=16) and sham-operated group (n=16) by random. Middle cerebral artery occlusion (MCAO) model was established with suture embolicmethod, sham-operated group were operated with nylon suture just put into external carotic artery, 1ug IGF-1 (5ul) was infused into the lateral ventricular in MCAO model rats, NS (5ul) were used in MCAO-control group to replace IGF-1. Every 4 rats (selected by random) in the three groups were sacrificed at 7d, 14d, 28d and 42d after cerebral middle artery occlusion operation (MCAO), respectively. To evalute the relationship between proliferation, migration and differentiation, bromodeoxyuridine (BrdU), high polysialylated neural cell adhesion molecular (PSA-NCAM), microtubule-associated protein (MAP2) and glial fibrillary acidic protein (GFAP) were choosed as the makers of proliferation, migration and differentiation, respectively. BrdU-labeled cells, PSA-NCAM-labeled cells, BrdU-labeled cells with PSA-NCAM expression (BrdU-PSA-NCAM-labeled cells), BrdU-labeled cells with MAP2 expression (BrdU-MAP2-labeled cells) and BrdU-labeled cells with GFAP expression (BrdU-GFAP-labeled cells) were identified by immunohisochemistry staining and double immunohischemistry staining.Experiment II: Health male SD rats were divided into young group (3 to4 months) and older group (1 year). Middle cerebral artery occlusion model was established with suture embolic method, lug IGF-1 (5ul) was infused into the lateral ventricular in MCAO model rats, NS (5ul) were used in control groups to replace IGF-1. The two groups were divided into young -treated group (n=12), young-control group (n=8), older-treated group (n=12) and older-control group(n=8) again. One half of the rats in the above four groups were sacrified at 7d , the other half were sacrificed at 28d after MCAO. Bromodeoxyuridin (BrdU) labeling method was choosed to identify the proliferating cells 7d and 28 d after MCAO. BrdU-labeled cells were identified by immunohisochemistryResults:Experiment I: BrdU-ladeled cells and PSA-NCAM-labeled cells increased approximately by 4.0-fold and 1.8-fold compared with the control groups respectively, 9.9-fold and 5.4-fold compared with sham-operated groups, both with a largest number at 7d after MCAO. BrdU-labeled cells with PSA-NCAM expression(BrdU-PSA-NCAM-labeled cells) were detected both in the SVZ and DG with a largest number of 7d after ischemia and gradually decrease after that. But BrdU-labeled cells with MAP2 and GFAP expressions (BrdU-MAP2-labeled cells and BrdU-GFAP-labeled cells) gradually increased from 14d after ischemia.Experiment II: The number of BrdU-labeled cells increased approximately 5.5-fold and 5.1-fold 7d after MCAO in young group and older group respectively, contrasted with the control group. The residual rates 28d after MCAO in young gro...
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