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首页> 外文期刊>Neurosurgery >Marrow Stromal Cell Transplantation after Traumatic Brain Injury Promotes Cellular Proliferation within the Brain.
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Marrow Stromal Cell Transplantation after Traumatic Brain Injury Promotes Cellular Proliferation within the Brain.

机译:颅脑创伤后的骨髓基质细胞移植促进了脑内细胞的增殖。

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OBJECTIVE: This study was designed to investigate the effects of intracerebral as well as intravenous administration of bone marrow stromal cells (MSCs) on endogenous cellular proliferation after traumatic brain injury (TBI). METHODS: Two experimental groups of Wistar rats were studied. One group received MSCs intracerebrally, and the other group received MSCs intravenously after injury by controlled cortical impact. MSCs were harvested from the bone marrow of male Wistar rats. For the intracerebral study, 24 male rats were divided into three groups (eight rats per group): rats injected with MSCs (1 x 10(6)) intracerebrally 1 day after TBI; 2) rats injected with phosphate-buffered saline intracerebrally 1 day after TBI; and 3) sham group not subjected to injury and not administered treatment. For the intravenous study, 10 female Wistar rats were injected 1 day after TBI with either MSCs (2 x 10(6)) (n = 5) or phosphate-buffered saline (n = 5) via the tail vein. Neurological function of the rats was evaluated with modified neurological severity scores and rotarod motor test. All rats were injected with bromodeoxyuridine intraperitoneally, to label the newly generating cells. Rats were killed 15 days after TBI, and coronal brain sections were stained immunohistochemically with diaminobenzidine to identify newly generating bromodeoxyuridine-positive cells. To study the differentiation of newly generating cells into neurons, sections were also double-stained for neuronal markers (Tuj1, doublecortin, NeuN) with fluorescein isothiocyanate. RESULTS: The data demonstrate that newly generating cells were mainly present in the subventricular zone, hippocampal formation, and boundary zone of contusion of both treated and control animals. Intracerebral MSC treatment significantly increased the progenitor cell proliferation in the subventricular zone and boundary zone compared with the controls, whereas intravenous MSC treatment enhanced this endogenous proliferation in subventricular zone, hippocampus, and boundaryzone. In both groups, some of the new cells revealed positive staining for neuronal markers. A statistically significant functional improvement was observed in both the intracerebrally as well as intravenously treated groups. CONCLUSION: Intracerebral and intravenous MSC administration promotes endogenous cellular proliferation after TBI in rats. This may contribute to the functional improvement observed in these rats.
机译:目的:本研究旨在研究脑外伤性脑损伤(TBI)后脑内以及静脉内给药骨髓基质细胞(MSC)对内源性细胞增殖的影响。方法:研究了Wistar大鼠的两个实验组。一组在脑内接受MSC,另一组在受到可控的皮层撞击后静脉接受MSC。从雄性Wistar大鼠的骨髓中收获MSC。对于脑内研究,将24只雄性大鼠分为三组(每组八只大鼠):在TBI后1天,脑内注射MSCs(1 x 10(6))的大鼠;和2)大鼠在TBI后1天脑内注射磷酸盐缓冲盐水。 3)假手术组未受伤,未给予治疗。对于静脉研究,在TBI后1天向10只雌性Wistar大鼠通过尾静脉注射MSC(2 x 10(6))(n = 5)或磷酸盐缓冲液(n = 5)。用改良的神经病学严重程度评分和轮足运动测试评估大鼠的神经功能。给所有大鼠腹膜内注射溴脱氧尿苷,以标记新生细胞。 TBI 15天后处死大鼠,用二氨基联苯胺对冠状脑切片进行免疫组织化学染色,以鉴定新产生的溴脱氧尿苷阳性细胞。为了研究新生细胞向神经元的分化,还用异硫氰酸荧光素对神经元标记(Tuj1,doublecortin,NeuN)进行了双染色。结果:数据表明,新生细胞主要存在于治疗和对照动物的脑室下区域,海马形成和挫伤边界区域。与对照组相比,脑内MSC治疗显着增加了脑室下区域和边界区域的祖细胞增殖,而静脉MSC治疗则增强了脑室内膜下区域,海马和边界区域的内源性增殖。在两组中,一些新细胞均显示出神经元标记物的阳性染色。在脑内和静脉内治疗组中均观察到统计学上显着的功能改善。结论:脑内和静脉内MSC治疗可促进大鼠TBI后内源性细胞增殖。这可能有助于在这些大鼠中观察到的功能改善。

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