Long-term recovery after bone marrow stromal cell treatment of traumatic brain injury in rats
Long-term recovery after bone marrow stromal cell treatment of traumatic brain injury in rats
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DOI：
10.3171/jns.2006.104.2.272
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发表时间：
2006-02-01
影响因子：
4.1
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
Object.本研究旨在观察骨髓基质细胞（BMSC）对大鼠创伤性脑损伤（TBI）后3个月的影响。40只成年雌性Wistar大鼠通过可控的皮质撞击受伤，1周后，静脉注射从雄性大鼠中获得的三种不同剂量的BMSC（每只动物2 × 10（6）、4 × 10（6）或8 × 10（6）细胞）中的一种。对照组大鼠接受磷酸盐缓冲盐水（PBS）。使用神经系统严重程度量表（NSS）研究这些大鼠的神经功能。伤后3个月处死大鼠，取脑组织行免疫组织化学染色，观察BMSCs的分布。通过定量酶联免疫吸附测定法分析额外的脑样品，以测量生长因子脑源性神经营养因子（BDNF）和神经生长因子（NGF）的表达。BMSC存在于受损的大脑中，并且在接受4 × 10（6）或8 × 10（6）的动物中，它们的数量明显更多。与接受2 × 106 BMSCs的动物相比，细胞主要分布在病变边界区周围。与对照动物相比，接受4 × 10（6）或8 × 10（6）BMSC的大鼠的功能结果明显更好，尽管在接受2 × 10（6）BMSC的动物中没有看到改善。所有剂量的BMSC均显著增加BDNF的表达，但不增加NGF的表达;然而，接受4 × 10（6）或8 × 10（6）BMSC的动物的这种增加显著大于对照组或接受2 × 10（6）BMSC的动物。总之，当在TBI后注射到大鼠中时，BMSC在3个月后存在于脑中，并显著改善功能结果。
Object. This study was designed to follow the effects of bone marrow stromal cell (BMSC) administration in rats after traumatic brain injury (TBI) for a 3-month period.Methods. Forty adult female Wistar rats were injured by a controlled cortical impact and, I week later, were injected intravenously with one of three different doses of BMSCs (2 X 10(6), 4 X 10(6), or 8 X 10(6) cells per animal) obtained in male rats. Control rats received phosphate-buffered saline (PBS). Neurological function in these rats was studied using a neurological severity scale (NSS). The rats were killed 3 months after injury, and immunohistochemical stains were applied to brain samples to study the distribution of the BMSCs. Additional brain samples were analyzed by quantitative enzyme-linked immunosorbent assays to measure the expression of the growth factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF).Three months after injury, BMSCs were present in the injured brain and their number was significantly greater in animals that received 4 X 10(6) or 8 X 10(6) BMSCs than in animals that received 2 X 106 BMSCs, The cells were primarily distributed around the lesion boundary zone. Functional outcome was significantly better in rats that received 4 X 10(6) or 8 X 10(6) BMSCs, compared with control animals, although no improvement was seen in animals that received 2 X 10(6) BMSCs. All doses of BMSCs significantly increased the expression of BDNF but not that of NGF; however, this increase was significantly larger in animals that received 4 X 10(6) or 8 X 10(6) BMSCs than in controls or animals that received 2 X 10(6) BMSCs.Conclusions. In summary, when injected in rats after TBI, BMSCs are present in the brain 3 months later and significantly improve functional outcome.