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脑出血后移植到大鼠脑内的间充质干细胞的分化及神经功能益处

Differentiation and neurological benefit of the mesenchymal stem cells transplanted into the rat brain following intracerebral hemorrhage.

作者信息

Zhang Huabiao, Huang Zhiyong, Xu Yuming, Zhang Suming

机构信息

Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China, 210029.

出版信息

Neurol Res. 2006 Jan;28(1):104-12. doi: 10.1179/016164106X91960.

Abstract

Spontaneous intracerebral hemorrhage (ICH) is often a fatal event. In a patient who survives the initial ictus, the resulting hematoma within brain parenchyma can trigger a series of events that lead to secondary insults and severe neurological deficits. Great efforts have been focused on searching for new approaches to help patients recover neurological function after ICH. Previous studies indicate that mesenchymal stem cells (MSCs) grafted into the ischemic rat brain can improve neurological function. However, there is no report regarding whether MSCs can be used in the same way to improve the neurological function after ICH. We generated the ICH model by injecting collagenase VII into rat brain. Subsequently, 5-bromo-2-deoxyuridine (BrdU)-labeled mesenchymal stem cells were delivered into the brain through carotid artery, cervical vein or lateral ventricle. The distribution and differentiation of MSCs were investigated by methods of immunohistochemistry. We found that MSCs were able to differentiate into neural cells in vitro as well as in the rat brain after ICH. The injected MSCs were able to migrate into hippocampus, blooding foci and ipsilateral cortex. In the hippocampus, MSCs differentiated into neurons; but in surrounding bleeding foci, they differentiated into neurons and astrocytes. In the ipsilateral cortex, MSCs differentiated into neurons, astrocytes and oligodendrocytes. Notably, the motor function of the rats in the carotid artery (CA) group and the lateral ventricle (LV) group improved significantly. Collectively, our study indicates that MSCs are able to differentiate into neural cells in the rat brain after ICH and can significantly improve motor function.

摘要

自发性脑出血(ICH)通常是致命事件。在最初发作后存活下来的患者中,脑实质内形成的血肿会引发一系列导致继发性损伤和严重神经功能缺损的事件。人们一直致力于寻找新方法来帮助脑出血患者恢复神经功能。先前的研究表明,移植到缺血大鼠脑内的间充质干细胞(MSCs)可改善神经功能。然而,关于间充质干细胞是否能以同样方式用于改善脑出血后的神经功能尚无报道。我们通过向大鼠脑内注射Ⅶ型胶原酶建立脑出血模型。随后,将5-溴-2-脱氧尿苷(BrdU)标记的间充质干细胞通过颈动脉、颈静脉或侧脑室注入脑内。采用免疫组织化学方法研究间充质干细胞的分布和分化情况。我们发现,间充质干细胞在体外以及脑出血后的大鼠脑内均能分化为神经细胞。注入的间充质干细胞能够迁移至海马体、出血灶和同侧皮质。在海马体中,间充质干细胞分化为神经元;但在周围出血灶中,它们分化为神经元和星形胶质细胞。在同侧皮质中,间充质干细胞分化为神经元、星形胶质细胞和少突胶质细胞。值得注意的是,颈动脉(CA)组和侧脑室(LV)组大鼠的运动功能有显著改善。总体而言,我们的研究表明,间充质干细胞在脑出血后能在大鼠脑内分化为神经细胞,并能显著改善运动功能。

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