Perinatal hypoxic/ischemic brain injury induces persistent production of striatal neurons from subventricular zone progenitors.
Ischemia-induced production of new striatal neurons in young and adult rodents has been studied. However, it is unclear whether neonatal hypoxic/ischemic (H/I) brain injury-induced neuronogenesis in the striatum is transient or sustained, nor has it been established whether these new neurons arise from progenitors within the striatum or from precursors residing in the adjacent subventricular zone. Here, we report that from 2 weeks to 5 months after H/I there are more doublecortin-positive (Dcx+) cells and Dcx+/NeuN+ cells in the damaged striatum compared to the contralateral striatum. After the S-phase marker 5-bromo-2'-deoxyuridine (BrdU) was injected at both short and long intervals (2 days and 2 months) after H/I to label newly born cells, more BrdU+/Dcx+ and BrdU+/NeuN+ cells were observed in the ipsilateral striatum compared to the contralateral striatum. Retroviral fate-mapping studies demonstrated that these newly born striatal neurons are generated from precursors within the subventricular zone. Altogether, these observations indicate the neonatal brain initiates a prolonged regenerative response from the precursors of the subventricular zone (SVZ) that results in persistent production of new striatal neurons.
Yang
Zhengang
Z
Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, PR China.
Levison
Steven W
SW
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D003342:Corpus Striatum / Q000166:cytology / Q000473:pathology*; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D002534:Hypoxia, Brain / Q000473:pathology*; D020547:Lateral Ventricles / Q000166:cytology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D015415:Biomarkers; D004268:DNA-Binding Proteins; C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009479:Neuropeptides; D009687:Nuclear Proteins; D001973:Bromodeoxyuridine