Reduced ischemic brain injury by partial rejuvenation of bone marrow cells in aged rats.
Reduced ischemic brain injury by partial rejuvenation of bone marrow cells in aged rats.
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DOI：
10.1038/jcbfm.2010.165
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发表时间：
2011-03
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影响因子：
--
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循环中的骨髓来源的未成熟细胞，包括内皮祖细胞，已被认为与微血管系统的动态平衡有关。循环内皮祖细胞水平降低与衰老和/或心血管危险因素有关，与一系列心血管疾病的不良临床结局相关。在这里，我们将年轻的卒中易感自发性高血压大鼠(SHR-SP)的骨髓细胞移植到老年SHR-SP中，后者没有受到放射或化疗的影响。移植后28天的受者外周血分析显示，5%的循环血细胞来自供者。移植后第30天诱导大鼠脑梗塞。移植年轻SHR-SP骨髓的动物显示，梗死区微血管密度增加，缺血性脑损伤减轻，神经功能改善。体外分析显示，与老年动物的细胞相比，暴露于幼年动物骨髓来源的单个核细胞的培养物内皮型一氧化氮合酶活性增强，而p38微管相关蛋白(MAP)激酶活性降低，后者与内皮细胞凋亡有关。我们的发现表明，用年轻动物的细胞部分恢复老龄大鼠的骨髓，可能在内皮/血管激活的水平上增强了对缺血损伤的反应，为改善慢性血管疾病提供了一种新的方法。
Circulating bone marrow-derived immature cells, including endothelial progenitor cells, have been implicated in homeostasis of the microvasculature. Decreased levels of circulating endothelial progenitor cells, associated with aging and/or cardiovascular risk factors, correlate with poor clinical outcomes in a range of cardiovascular diseases. Herein, we transplanted bone marrow cells from young stroke-prone spontaneously hypertensive rats (SHR-SP) into aged SHR-SP, the latter not exposed to radiation or chemotherapy. Analysis of recipient peripheral blood 28 days after transplantation revealed that 5% of circulating blood cells were of donor origin. Cerebral infarction was induced on day 30 posttransplantation. Animals transplanted with bone marrow from young SHR-SP displayed an increase in density of the microvasculature in the periinfarction zone, reduced ischemic brain damage and improved neurologic function. In vitro analysis revealed enhanced activation of endothelial nitric oxide synthase and reduced activation p38 microtubule-associated protein (MAP) kinase, the latter associated with endothelial apoptosis, in cultures exposed to bone marrow-derived mononuclear cells from young animals versus cells from aged counterparts. Our findings indicate that partial rejuvenation of bone marrow from aged rats with cells from young animals enhances the response to ischemic injury, potentially at the level of endothelial/vascular activation, providing insight into a novel approach ameliorate chronic vascular diseases.
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
4.8
作者：
Sonntag, WE;Lynch, CD;Hutchins, PM
通讯作者：
Hutchins, PM
DOI：
10.1097/00004647-199802000-00008
发表时间：
1998-02-01
影响因子：
6.3
作者：
Loddick, SA;Turnbull, AV;Rothwell, NJ
通讯作者：
Rothwell, NJ
影响因子：
20.3
作者：
Majka, M;Janowska-Wieczorek, A;Ratajczak, MZ
通讯作者：
Ratajczak, MZ
影响因子：
37.8
作者：
Schmidt-Lucke, C;Rössig, L;Zeiher, AM
通讯作者：
Zeiher, AM