Neonatal hypoxic-ischemic brain injury activates hippocampal stem/progenitor cells
Birth asphyxia remains a frequent cause of perinatal morbidity and mortality. During perinatal hypoxic-ischemic (HI) brain injury neuronal cells are damaged and lose their function or die. Recently, it has become clear that ischemic brain injury stimulates neural stem cell proliferation and differentiation in cerebral neurogenic areas – subventricular zone (SVZ) and dentate gyrus (DG) of the hippocampus frequently injured after the perinatal HI. There is a tremendous speculation, that the induction of these progenitors after injury may represent an endogenous mechanism for brain regeneration. To study the response of hippocampal progenitors to neonatal HI brain damage, we utilized an established model of HI induced in rats of postnatal day 7 (PND7). The left common carotid artery was ligated and then after 60 min of recovery, the animals were exposed to hypoxia (7.4% oxygen for 75 min). The hypoxic undamaged hemisphere served as control for developmental modification. In addition, age-matched sham-operated rats were also used as controls. At 4, 10, 14, and 21 days following hypoxia, pups were perfused transcardially with PBS followed by 4% PFA. To determine the proliferation profile animals were injected with BrdU (50 mg/ kg) at various days after HI and immunopositive cells were analyzed the next day. At 4 - 14 days after HI the presence of BrdUpositive cells was seen in both, ipsi- and contralateral hemispheres, with the greatest number of dividing cells in the ischemic side. Thereafter, cell proliferation appeared to be reduced. The labeling pattern revealed structure-dependent differences. At 4 days after the insult the highest density of cells incorporating BrdU was seen in hilus, whereas at longer survival time the majority of labeled cells were located in the DG. To confirm that the BrdU-positive cells represent dividing progenitors we used double staining: BrdU/Ki67, BrdU/PSA-NCAM and immature neuronal marker - DCX.
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