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围产期缺氧/缺血性脑损伤诱导脑室下区祖细胞持续产生纹状体神经元。

Perinatal hypoxic/ischemic brain injury induces persistent production of striatal neurons from subventricular zone progenitors.

作者信息

Yang Zhengang, Levison Steven W

机构信息

Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, PR China.

出版信息

Dev Neurosci. 2007;29(4-5):331-40. doi: 10.1159/000105474.

DOI:10.1159/000105474
PMID:17762201
Abstract

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.

摘要

人们已经对年轻和成年啮齿动物中缺血诱导产生新的纹状体神经元进行了研究。然而,尚不清楚新生儿缺氧缺血(H/I)性脑损伤诱导的纹状体神经发生是短暂的还是持续的,也不清楚这些新神经元是源自纹状体内的祖细胞还是源自相邻脑室下区的前体细胞。在此,我们报告,与对侧纹状体相比,在H/I后2周~5个月期间,受损纹状体中双皮质素阳性(Dcx+)细胞和Dcx+/NeuN+细胞更多。在H/I后短期和长期(2天和2个月)注射S期标记物5-溴-2'-脱氧尿苷(BrdU)以标记新生细胞后,与对侧纹状体相比,在同侧纹状体中观察到更多的BrdU+/Dcx+和BrdU+/NeuN+细胞。逆转录病毒命运图谱研究表明,这些新生的纹状体神经元是由脑室下区内的前体细胞产生的。总之,这些观察结果表明,新生大脑启动了来自脑室下区(SVZ)前体细胞的长期再生反应,从而导致新的纹状体神经元持续产生。

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