Intravenous administration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury
Intravenous administration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury
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DOI：
10.1089/089771504772695922
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发表时间：
2004-01-01
影响因子：
4.2
通讯作者：
Chopp, M
中科院分区：
文献类型：
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作者：
Mahmood, A;Lu, DY;Chopp, M
本研究旨在探讨静脉注射骨髓基质细胞（MSCs）对创伤性脑损伤（TBI）后大鼠脑组织生长因子表达的影响。免疫组织化学检测移植间充质干细胞的命运和生长因子的表达。此外，采用酶联免疫吸附法（ELISA）定量测定生长因子水平。所研究的生长因子包括神经生长因子（NGF）、脑源性神经营养因子（BDNF）和碱性成纤维细胞生长因子（bFGF）。在免疫组织化学研究中，12只雄性Wistar大鼠遭受TBI后分为三组，第一组不治疗，第二组接受生理盐水（安慰剂），第三组在TBI后1天静脉注射MSCs。采用Rotarod运动试验和改良神经功能严重程度评分法研究大鼠神经功能。TBI后15天处死动物，免疫组化染色脑切片，研究MSCs的分布以及生长因子NGF、BDNF和bFGF的表达。为了进行定量分析，第二组雄性Wistar大鼠（n = 18）遭受TBI，然后在损伤1天后注射生理盐水（n = 9）或MSCs （n = 9）。这些大鼠在TBI后的第2、5和8天被处死，脑提取物用于测量NGF、BDNF和bFGF。我们发现，移植后，MSCs优先迁移到受损半球，与对照组相比，MSCs治疗大鼠的功能结局有统计学上显著改善。治疗组和对照组损伤大鼠脑内均有NGF、BDNF和bFGF的表达；而定量ELISA研究显示，治疗组NGF和BDNF的表达显著升高（p < 0.05）。本研究表明，脑外伤后静脉给药MSCs可增加生长因子（NGF、BDNF）的表达，这可能有助于这些大鼠功能结果的改善。
This study was designed to investigate the effects of intravenous administration of marrow stromal cells (MSCs) on the expression of growth factors in rat brain after traumatic brain injury (TBI). The fate of transplanted MSCs and expression of growth factors was examined by immunohistochemistry. In addition, the level of growth factors was measured quantitatively using enzyme linked immunosorbent assay (ELISA). Growth factors that were studied included nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF). For immunohistochemical studies, 12 male Wistar rats were subjected to TBI and then divided into three groups with the first group receiving no treatment, the second group receiving saline (placebo) and the third group receiving MSCs intravenously 1 day after TBI. The neurological function of rats was studied by using Rotarod motor test and modified neurological severity scores. The animals were sacrificed 15 days after TBI and brain sections stained by immunohistochemistry to study the distribution of MSCs as well as expression of growth factors NGF, BDNF, and bFGF. For quantitative analysis, a second set of male Wistar rats (n = 18) was subjected to TBI and then injected with either saline (n = 9) or MSCs (n = 9) 1 day after injury. These rats were sacrificed on days 2, 5, and 8 after TBI and brain extracts used to measure NGF, BDNF, and bFGF. We found that after transplantation, MSCs preferentially migrated into the injured hemisphere and there was a statistically significant improvement in the functional outcome of MSC-treated rats compared to control rats. NGF, BDNF, and bFGF were expressed in the injured brain of both treated as well as control rats; however, quantitative ELISA studies showed that expression of NGF and BDNF was significantly increased (p < 0.05) in the treated group. This study shows that intravenous administration of MSCs after TBI increases the expression of growth factors (NGF, BDNF), which possibly contributes to the improvement in functional outcome seen in these rats.