在大鼠大脑急性缺血再灌注过程中,不同来源的多能间充质基质细胞可减少海马CA1区的反应性胶质增生

Q4 Medicine
Sergii Konovalov, Nina Konovalova, Vasyl Moroz, O. Deryabina, Olena Toporova, A. Tochylovsky, Vitaly Kordium
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引用次数: 0

摘要

急性脑血管疾病的神经保护疗法直接旨在保护半影区的神经元,但同时也强调受影响区域胶质细胞生成的重要性。神经胶质细胞反应迅速,对脑缺血损伤高度敏感。最近的实验研究表明,多能间充质基质细胞(MMSCs)在中风中的应用成功地调节了小胶质细胞的活化。本研究旨在探讨不同来源的间充质干细胞、间充质干细胞裂解液和柠檬胆碱对大鼠脑缺血再灌注模型中神经胶质成分的影响。材料与方法实验对象为 190 只雄性 Wistar 大鼠,年龄 4 个月,体重 160-190 克。在通过双侧颈内动脉闭塞 20 分钟建立脑缺血再灌注模型后,给大鼠静脉注射来源于人 Wharton 胶冻、人脂肪组织和大鼠 Wharton 胶冻的 MMSCs,剂量为每只动物 106 个细胞。其他组接受胎鼠成纤维细胞(106 个细胞/只动物,0.2 毫升生理溶液)和人的沃顿果冻裂解物,剂量为每只动物 0.2 毫升。对照组动物静脉注射 0.2 毫升生理溶液。最后一组大鼠接受单剂量参考药物柠檬胆碱,剂量为 250 毫克/千克。第 7 天和第 14 天,使用免疫组化检查和共聚焦显微镜定量评估 CA1 海马区切片中表达星形胶质细胞(GFAP)、小胶质细胞(Iba1)和少突胶质细胞(Rip)标记的细胞的面积和荧光强度。结果大鼠脑缺血再灌注后第 7 天和第 14 天,GFAP 阳性星形胶质细胞和 Iba1 阳性小胶质细胞的荧光强度增加,表明海马 CA1 区存在明显的反应性星形胶质细胞增多和小胶质细胞活化。同时,缺血再灌注对脑片中 Rip 阳性少突胶质细胞的含量有显著影响。所有治疗方法(移植不同来源的 MMSCs、其裂解物或参考药物柠檬胆碱)都具有细胞保护作用,在损伤后第 7 天和第 14 天都减少了反应性星形胶质细胞和小胶质细胞的增生。使用人类沃顿氏果冻间充质干细胞进行治疗的效果最佳。脑缺血再灌注通过激活海马各层中 GFAP 和 Iba1 阳性的神经胶质细胞诱导反应性神经胶质增生。在损伤建模后的第 7 天和第 14 天,应用来自人 Wharton's jelly 和胎鼠成纤维细胞的间充质干细胞可显著降低反应性胶质增生的强度。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multipotent mesenchymal stromal cells of various origins reduce reactive gliosis in the hippocampal CA1 area during acute ischemia-reperfusion of the rat brain
Neuroprotective therapy in acute cerebrovascular disorders is directly aimed at preserving neurons in the penumbra zone, but it also emphasizes the importance of gliogenesis in the affected area. Glial cells exhibit rapid reactivity and are highly sensitive to cerebral ischemic damage. Recent experimental studies have demonstrated the successful application of multipotent mesenchymal stromal cells (MMSCs) in stroke to modulate microglial activation. The aim of the study was to investigate the impact of MMSCs of different origins, MMSC lysate, and citicoline on glial components in a model of cerebral ischemia-reperfusion in rats. Materials and methods. The experiments were conducted on 190 male Wistar rats aged 4 months, weighing 160-190 g. After modeling cerebral ischemia-reperfusion through bilateral 20-minute occlusion of the internal carotid arteries, rats were intravenously administered MMSCs derived from human Wharton’s jelly, human adipose tissue, and rat Wharton’s jelly at a dose of 106 cells per animal. Other groups received fetal rat fibroblasts (106 cells/animal in 0.2 ml of physiological solution) and lysate from human Wharton’s jelly at a dose of 0.2 ml per animal. Control animals received 0.2 ml of physiological solution intravenously. The last group of rats received a single dose of the reference drug citicoline at a dose of 250 mg/kg. On the 7th and 14th days, the area and fluorescence intensity of cells expressing markers of astrocytes (GFAP), microglia (Iba1), and oligodendrocytes (Rip) were quantitatively assessed in CA1 hippocampal region slices using immunohistochemical examination and confocal microscopy. Results. On the 7th and 14th days after cerebral ischemia-reperfusion in rats, the intensity of fluorescence of GFAP-positive astrocytes and Iba1-positive microglial cells increased, indicating pronounced reactive astrogliosis and microglial activation in the CA1 region of the hippocampus. Meanwhile, ischemia-reperfusion had a significant impact on the content of Rip-positive oligodendrocytes in brain slices. The application of all treatments (transplantation of MMSCs of different origins, their lysate, or the reference drug citicoline) had a cytoprotective effect, reducing reactive astrogliosis and microgliosis both on the 7th and 14th days after injury. The best result was demonstrated with the treatment using MSCs from human Wharton’s jelly.s. Conclusion. Cerebral ischemia-reperfusion induces reactive gliosis through the activation of GFAP- and Iba1-positive glial cells in all layers of the hippocampus. The application of MSCs from human Wharton’s jelly and fetal rat fibroblasts significantly reduces its intensity on both the 7th and 14th days after injury modeling.
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来源期刊
Cell and Organ Transplantology
Cell and Organ Transplantology Medicine-Transplantation
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