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首页> 外文期刊>Translational Stroke Research >Histopathological Investigation of Different MCAO Modalities and Impact of Autologous Bone Marrow Mononuclear Cell Administration in an Ovine Stroke Model
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Histopathological Investigation of Different MCAO Modalities and Impact of Autologous Bone Marrow Mononuclear Cell Administration in an Ovine Stroke Model

机译:绵羊中风模型中不同MCAO模式的组织病理学研究以及自体骨髓单个核细胞给药的影响

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摘要

Translational researchers and clinicians recommend the use of large animal models in preclinical stroke research. This represents an important part of a strategy aiming to prevent past translational failures in future therapeutic developments. Thirty-five Merino rams were subjected to sham surgery (n = 3), one-branch middle cerebral artery occlusion (MCAO, n = 8) or total MCAO (n = 24). Twelve animals from the latter group received intravenous administration of 4 × 106 autologous mononuclear bone marrow cells (BM MNC) per kilogram 24 h after total MCAO. Animals were sacrificed at day 49 post MCAO. Histological investigations were performed to reveal (1) the impact of different MCAO modalities on a cellular level and (2) the influence of BM MNC therapy following stroke. Clear differences between one-branch and total MCAO were observed histologically with results being comparable to those seen in human patients. BM MNC treatment reduced final lesion extension, lymphocytic infiltration and axonal degeneration after MCAO. The sheep model may represent a feasible tool for translational stroke research as pathohistological findings mimic the situation in humans. Histological evidence was found for beneficial impact of autologous BM MNC therapy. Further studies are needed to assess the neurofunctional impact of the approach in the gyrencephalic brain.
机译:转化研究人员和临床医生建议在临床中风研究之前使用大型动物模型。这代表了旨在防止将来的治疗发展中过去的翻译失败的策略的重要部分。对三十五只美丽诺公羊进行了假手术(n = 3),大脑中动脉一分支闭塞(MCAO,n = 8)或总MCAO(n = 24)。后一组中的十二只动物在总MCAO后24小时每公斤静脉内注射4×106 自体单核骨髓细胞(BM MNC)。 MCAO后第49天处死动物。进行组织学研究以揭示(1)不同MCAO方式对细胞水平的影响,以及(2)中风后BM MNC治疗的影响。在组织学上观察到一分支和总MCAO之间的明显差异,结果与人类患者中观察到的结果相当。 BM MNC治疗减少了MCAO后的最终病变扩展,淋巴细胞浸润和轴突变性。绵羊模型可能代表了翻译性卒中研究的可行工具,因为病理组织学发现模仿了人类的情况。已发现组织学证据对自体BM MNC治疗的有益影响。需要进一步的研究来评估该方法对脑性脑的神经功能影响。

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