The combination of stem cell factor and granulocyte-colony stimulating factor for chronic stroke treatment in aged animals.

Chun-Shu Piao, Maria E Gonzalez-Toledo, Xi Gu, Li-Ru Zhao
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引用次数: 14

Abstract

Unlabelled:

Background: Stroke occurs more frequently in the elderly population and presents the number one leading cause of persistent disability worldwide. Lack of effective treatment to enhance brain repair and improve functional restoration in chronic stroke, the recovery phase of stroke, is a challenging medical problem to be solved in stroke research. Our early study has revealed the therapeutic effects of stem cell factor (SCF) in combination with granulocyte-colony stimulating factor (G-CSF) (SCF+G-CSF) on chronic stroke in young animals. However, whether this treatment is effective and safe to the aged population remains to be determined.

Methods: Cortical brain ischemia was produced in aged C57BL mice or aged spontaneously hypertensive rats. SCF+G-CSF or equal volume of vehicle solution was subcutaneously injected for 7 days beginning at 3-4 months after induction of cortical brain ischemia. Using the approaches of biochemistry assays, flow cytometry, pathology, and evaluation of functional outcome, several doses of SCF+G-CSF have been examined for their safety and efficiency on chronic stroke in aged animals.

Results: All tested doses did not show acute or chronic toxicity in the aged animals. Additionally, SCF+G-CSF treatment in chronic stroke of aged animals mobilized bone marrow stem cells and improved functional outcome in a dose-dependent manner.

Conclusions: SCF+G-CSF treatment is a safe and effective approach to chronic stroke in the aged condition. This study provides important information needed for developing a new therapeutic strategy to improve the health of older adults with chronic stroke.

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干细胞因子联合粒细胞集落刺激因子治疗老年动物慢性脑卒中。
背景:中风在老年人群中更为常见,是世界范围内造成持续性残疾的头号原因。在脑卒中恢复期的慢性脑卒中中,缺乏有效的治疗方法来增强脑修复和改善功能恢复,是脑卒中研究中亟待解决的医学难题。我们的早期研究揭示了干细胞因子(SCF)联合粒细胞集落刺激因子(G-CSF) (SCF+G-CSF)对幼龄动物慢性卒中的治疗作用。然而,这种治疗方法对老年人群是否有效和安全仍有待确定。方法:老龄C57BL小鼠和老年自发性高血压大鼠脑皮质缺血。在脑皮质缺血诱导后3-4个月开始皮下注射SCF+G-CSF或等体积的载体溶液,持续7天。利用生物化学分析、流式细胞术、病理学和功能结果评估的方法,研究了几种剂量的SCF+G-CSF对老年动物慢性中风的安全性和有效性。结果:所有试验剂量对老年动物均无急性或慢性毒性。此外,SCF+G-CSF治疗老年动物慢性卒中可调动骨髓干细胞,并以剂量依赖的方式改善功能结局。结论:SCF+G-CSF治疗老年慢性脑卒中安全有效。这项研究为开发一种新的治疗策略来改善老年慢性中风患者的健康提供了重要的信息。
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