Beneficial effects of hematopoietic growth factor therapy in chronic ischemic stroke in rats
Beneficial effects of hematopoietic growth factor therapy in chronic ischemic stroke in rats
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DOI：
10.1161/strokeaha.107.486217
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发表时间：
2007-10-01
期刊：
影响因子：
8.3
通讯作者：
Kessler, John A.
中科院分区：
文献类型：
--
作者：
Zhao, Li-Ru;Berra, Hector H.;Kessler, John A.
背景和目的-脑卒中是全球成人残疾的主要原因。目前，对中风幸存者没有有效的治疗方法。干细胞因子（SCF）和粒细胞集落刺激因子（G-CSF）是调节造血的生长因子。我们以前观察到SCF和G-CSF对急性脑缺血具有神经保护和功能作用。在本研究中，SCF和G-CSF对慢性脑缺血的有益作用被determined.Methods - SCF，G-CSF，或SCF+G-CSF皮下注射到大鼠3.5个月后，诱导缺血性中风大脑中动脉闭塞。神经功能缺损通过肢体放置试验和足部错误试验随时间推移进行评估。治疗19周后行场诱发电位检查。使用连续冠状切片进行组织学检查，发现SCF+G-CSF治疗的大鼠在注射后1周、5周和17周出现显著的功能改善。SCF单独使用也能改善功能结局，但不如SCF+G-CSF稳定。在G-CSF处理的大鼠中未观察到功能益处。场诱发电位研究进一步证实了行为学数据，即在受损的大鼠脑中重建了正常的神经元活动模式，并具有良好的功能结果。有趣的是，梗死体积也显着减少SCF+G-CSF-treated rats.Conclusion -这些数据提供了第一个证据表明，在慢性脑缺血的功能恢复可以实现造血生长因子。
Background and Purpose - Stroke is the leading cause of adult disability worldwide. Currently, there is no effective treatment for stroke survivors. Stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) are the growth factors regulating hematopoiesis. We have previously observed that SCF and G-CSF have neuroprotective and functional effects on acute brain ischemia. In the present study, the beneficial effects of SCF and G-CSF on chronic brain ischemia were determined.Methods - SCF, G-CSF, or SCF+G-CSF was administered subcutaneously to rats 3.5 months after induction of ischemic stroke by middle cerebral artery occlusion. Neurological deficits were evaluated by limb placement test and foot fault test over time. Field-evoked potential was performed 19 weeks after treatment. Infarct volume was histologically determined using serial coronal sections.Results - Significant functional improvement was seen in SCF+G-CSF-treated rats 1, 5, and 17 weeks after injections. SCF alone also improved functional outcome, but it did not show as stable improvement as SCF+G-CSF. No functional benefit was seen in G-CSF-treated rats. Field-evoked potential studies further confirmed the behavioral data that the normal pattern of neuronal activity was reestablished in the lesioned brain of the rats with good functional outcome. Interestingly, infarction volume was also significantly reduced in SCF+G-CSF-treated rats.Conclusion - These data provide first evidence that functional restoration in chronic brain ischemia can be attained using hematopoietic growth factors.