Chou Jenny, Harvey Brandon K, Chang Chen-Fu, Shen Hui, Morales Marisela, Wang Yun
National Institute on Drug Abuse, IRP, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
J Neurol Sci. 2006 Jan 15;240(1-2):21-9. doi: 10.1016/j.jns.2005.08.015. Epub 2005 Oct 19.
Previous reports have indicated that the expression of bone morphogenetic protein-7 (BMP7) is enhanced after ischemic injury in brain. This upregulation may induce endogenous neurorepair in the ischemic brain. The purpose of this study was to examine neuroregenerative effects of BMP7 after ischemia-reperfusion injury. Adult Sprague-Dawley rats were anesthetized with chloral hydrate. Right middle cerebral artery (MCA) was transiently ligated with 10-O suture for 1 h. One day after MCA occlusion, vehicle or BMP7 was infused to the contralateral cerebral ventricle. To identify possible neurogenesis, bromodeoxyurindine (BrdU) was systemically injected on the fourth and fifth days after MCA occlusion. Animals treated with BMP7 showed a rapid correction of body asymmetry and neurological deficits, suggesting BMP7 facilitates recovery after stroke. Animals were sacrificed at 1 month after stroke and brains were analyzed using immunohistological techniques. BMP7 treatment enhanced immunoreactivity of BrdU in the subventricular zone, lesioned cortex, and corpus callosum. These BrdU-positive cells co-labeled with nestin and NeuN. Our behavioral and anatomical data suggest that BMP7 promotes neuroregeneration in stroke animals, possibly through the proliferation of new neuronal precursors after ischemia.
先前的报告表明,脑缺血损伤后骨形态发生蛋白-7(BMP7)的表达会增强。这种上调可能会诱导缺血性脑内的内源性神经修复。本研究的目的是检测BMP7在缺血再灌注损伤后的神经再生作用。成年Sprague-Dawley大鼠用氯水合醛麻醉。用10-O缝线将右侧大脑中动脉(MCA)短暂结扎1小时。MCA闭塞后一天,将载体或BMP7注入对侧脑室。为了确定可能的神经发生,在MCA闭塞后的第四和第五天全身注射溴脱氧尿苷(BrdU)。用BMP7治疗的动物身体不对称和神经功能缺损迅速得到纠正,这表明BMP7有助于中风后的恢复。中风后1个月处死动物,并用免疫组织学技术分析大脑。BMP7治疗增强了脑室下区、受损皮质和胼胝体中BrdU的免疫反应性。这些BrdU阳性细胞与巢蛋白和神经元核抗原共同标记。我们的行为和解剖学数据表明,BMP7可能通过缺血后新神经元前体细胞的增殖促进中风动物的神经再生。