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Apoptosis, Proliferation And Differentiation Of Neural Stem Cells In The SVZ Of The Neonatal Rats With Hypoxic-ischemia

Posted on:2007-10-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:S D CuiFull Text:PDF
GTID:1104360212484740Subject:Academy of Pediatrics
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Objectives:To investigate the changes of neural stem cells in the subventricular zone in the neonatal rats of ischemic brain injury, we establish a model of ischemic brain injury in 3-day-old rats; to understand the mechanism of progressive premature brain injury after ischemia and to provide the experimenting evidence of treating time window, we observe the changes of the number of the apoptotic cells in the subventricular zone of the 3-day-old rats after bilateral common artery of occlusion (BCAO); to provide the experimenting evidences for inducing the self neural stem cells in the subventricular zone to treat the premature brain injury after ischemia, we observe the changes of proliferating cells in the subventricular zone of the 3-day-old rats after BCAO; to progressively knowledge the mechanism of the birth of new neural stem cells and provide the experimental bases for investigating the function of newborn neural cells, we observe the changes of the newborn neural cells in the different locations of brain after BCAO, which may be derived from the subventricular zone.Methods: 3-day-old rats were divided into two groups: the controlling group and the experimenting group. Rats in the experimenting group were subjected to bilateral common arteries occlusion; rats in controlling group were not. We observed and calculated the body weight , brain weight , the size of lateral ventricle, the height of the corpus callosum above the lateral ventricle, the numbers of myelin sheath in stritum by luxol fast blue staining; observed and calculated the apoptotic cells by TUNEL in the dorsolateral subventricular zone(SVZdl) and the anterior subventricular zone(SVZa) ; observed and calculated the numbers of proliferating cells in the subventricular zone Which DNA is combined with BrdU in S phase in the 3-day-old rats after BCAO; observed and calculated the newborn neural cells in the different locations of brain which were double marked BrdU and the other mark(04/TuJ1/GFAP). Results: From the time point of 1 week of postischemia in the rats ofexperimenting group, the size of lateral ventricle progressively enlarges , the height of the corpus callosum begins to thinner than that of the controlling group, the numbers of myelin sheath become fewer than those of the controlling group; at the time point of 48h, 72h, 1w of postischemia in the rats of experimenting group , the numbers of the apoptotic cells in the SVZdl and SVZa are more than those in the controlling group. The numbers of the apoptotic cells at the time point of 72h of postischemia are the most prominent (SVZdl: 87.0±11.5 vs 60.9 ± 7.1; SVZa( coronal axis): 86.1±5.5 vs 56.4 ± 5.6; SVZa (sagittal axis) 69.1±3.5 vs 44.0 ± 2.3, p<0.01); at the time point of 4d, 7d, 10d, 14d of postischemia in the rats of experimenting group , the numbers of the BrdU+ cells in the SVZdl and SVZa are more than those in the controlling group, the numbers of the BrdU+ cells in the SVZdl at the time point of 4d of postischemia are the most prominent(253. 1±49.2 vs 133.5 ± 17.7, P value<0.01), the numbers of the BrdU+ cells in the SVZa at the time point of 7d of postischemia are the most prominent(233.0 ± 11.6 vs 110.4 ± 48.4, P value<0.01); at the time point of 35d of postischemia, the numbers of BrdU+/TuJl±cells in the OB , cortical plate, striatum of the experimenting group are more than those of the controlling group, the numbers of BrdU+/04±cells in the corpus callosum,OB, striatum of the experimenting group are more than those of the controlling group ; the numbers of BrdU+/GFAP±cells in the corpus callosum , OB , striatum of the experimenting group are more than those of the controlling group. Conclusions: The ischemia newborn rat after BCAO is the appropriate model of brain white matter injury ; the cells in the subventricular zone are susceptible to ischemia, which maybe result in the less regenerating cells in white matter; 48-72h of postischemia in the premature rats maybe the treating time window; the numbers of proliferating cells increase in the subventricular zone at the time point 4-7d of postischemia in the premature rats, which maybe the best treating time window of inducing self stem cells to repair the brain injury; after BCAO , the new proliferating cells can be differentiated into new neurons , atrocytes , oligodendrocytes, which maybe indicate the real repairing capacity of the neural stem cells from SVZ.
Keywords/Search Tags:BCAO, hypoxia/ischemia, brain white matter injury, subventricular zone, proliferation, differentiation, apoptosis
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