Enriched environment increases neural stem/progenitor cell proliferation and neurogenesis in the subventricular zone of stroke-lesioned adult rats
Enriched environment increases neural stem/progenitor cell proliferation and neurogenesis in the subventricular zone of stroke-lesioned adult rats
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DOI：
10.1161/01.str.0000166197.94147.59
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发表时间：
2005-06-01
期刊：
影响因子：
8.3
通讯作者：
Eriksson, PS
中科院分区：
文献类型：
--
作者：
Komitova, M;Mattsson, B;Eriksson, PS
背景和目的--成人脑室下区被认为是神经前体的内源性来源，可被招募到邻近的损毁区域。通过结扎纹状体分支远端大脑中动脉的方法，建立成年自发性高血压大鼠大脑皮质梗塞模型，然后将动物置于标准或丰富的环境中，存活5周。在缺血后第一周给予胸腺嘧啶核苷类似物溴脱氧尿苷。用Ki67和磷酸化组蛋白H3(细胞增殖)、SOX-2(神经干/祖细胞)、溴脱氧尿苷(慢周期、非迁移性假定的神经干细胞)和双重皮质素(新生未成熟神经元)等细胞特异性标记物研究了脑室下区神经干/祖细胞和神经元前体的产生。卒中五周后，标准环境中的卒中大鼠与非卒中大鼠相比，脑室下区的增殖程度较低。脑缺血后丰富的环境使细胞增殖水平正常化，溴脱氧尿嘧啶核苷评估的神经干细胞数量增加，双皮质激素阳性的神经母细胞增多，并沿着向脑梗塞的迁移链延伸。结论丰富的环境增加了皮质卒中后5周成人脑室下区神经干/祖细胞库和神经发生。这可能对组织再生具有潜在的重要性。
Background and Purpose - The subventricular zone in the adult brain is identified as an endogenous resource of neuronal precursors that can be recruited to adjacent lesioned areas. The hypothesis was tested that postischemic environmental enrichment might enhance subventricular zone cell genesis.Methods - A cortical infarct was induced in adult spontaneously hypertensive rats by ligating the middle cerebral artery distal to the striatal branches, after which animals were housed in either standard or enriched environment and allowed to survive for 5 weeks. The thymidine analogue bromodeoxyuridine was administered during the first postischemic week. The generation of neural stem/progenitor cells and neuronal precursors in the subventricular zone were studied with cell specific markers such as Ki67 and phosphorylated histone H3 ( cell proliferation), Sox-2 ( neural stem/ progenitor cells), bromodeoxyuridine ( slowly cycling, nonmigratory putative neural stem cells), and doublecortin ( newborn immature neurons).Results - Proliferating cells in the subventricular zone were identified as chiefly neural progenitors but also putative neural stem cells and neuronal precursors. Five weeks after stroke, proliferation in the subventricular zone was lower in stroke-lesioned rats housed in standard environment compared with nonlesioned rats. Postischemic environmental enrichment normalized cell proliferation levels, increased the numbers of putative neural stem cells as assessed with bromodeoxyuridine, and increased doublecortin-positive neuroblasts, which extended in migratory chains toward the infarct.Conclusions - Enriched environment increased the neural stem/ progenitor cell pool and neurogenesis in the adult subventricular zone 5 weeks after a cortical stroke. This might be of potential importance for tissue regeneration.