Zhao Li-Ru, Berra Hector H, Duan Wei-Ming, Singhal Seema, Mehta Jayesh, Apkarian A Vania, Kessler John A
Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, Ill, USA.
Stroke. 2007 Oct;38(10):2804-11. doi: 10.1161/STROKEAHA.107.486217. Epub 2007 Aug 30.
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.
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.
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.
These data provide first evidence that functional restoration in chronic brain ischemia can be attained using hematopoietic growth factors.
中风是全球成年人残疾的主要原因。目前，对于中风幸存者尚无有效的治疗方法。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。我们之前观察到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，确定了SCF和G-CSF对慢性脑缺血的有益作用。
在大脑中动脉闭塞诱导缺血性中风3.5个月后，对大鼠皮下注射SCF、G-CSF或SCF+G-CSF。随着时间的推移，通过肢体放置试验和足部失误试验评估神经功能缺损。治疗19周后进行场诱发电位检查。使用连续冠状切片通过组织学方法确定梗死体积。
在注射后1、5和17周，SCF+G-CSF治疗的大鼠出现了显著的功能改善。单独使用SCF也改善了功能结局，但不如SCF+G-CSF那样稳定。G-CSF治疗的大鼠未观察到功能益处。场诱发电位研究进一步证实了行为学数据，即功能结局良好的大鼠受损大脑中重新建立了正常的神经元活动模式。有趣的是，SCF+G-CSF治疗的大鼠梗死体积也显著减小。
这些数据首次证明，使用造血生长因子可实现慢性脑缺血的功能恢复。
