Intravenous administration of bone morphogenetic protein-7 after ischemia improves motor function in stroke rats
Intravenous administration of bone morphogenetic protein-7 after ischemia improves motor function in stroke rats
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DOI：
10.1161/01.str.0000051507.64423.00
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发表时间：
2003-02-01
期刊：
影响因子：
8.3
通讯作者：
Wang, Y
中科院分区：
文献类型：
--
作者：
Chang, CF;Lin, SZ;Wang, Y
背景和目的：我们和其他人先前报道了在大脑中动脉闭塞（MCAO）前给予骨形态发生蛋白-7 （BMP-7）可减少脑缺血损伤。最近的研究表明，BMP受体在脑缺血后表达上调。这种上调可能会促进缺血脑的内源性神经修复。本研究的目的是确定缺血/再灌注损伤后肠外给予BMP-7的神经再生作用。方法：用水合氯醛麻醉成年sd大鼠。大脑中动脉被通过右颈内动脉插入的细丝短暂阻塞。缺血60分钟后取出纤维，以便再灌注。部分动物在MCAO后24小时处死，检测BMP-7 mRNA的表达。其他动物在MCAO后24小时接受单剂量静脉注射BMP-7或载体，并用于随后的行为研究和BMP-7免疫染色。结果：未处理动物MCAO后24小时bmp -7 mRNA表达上调。静脉注射BMP-7的动物在MCAO后第6天，海马/齿状体缺血侧的BMP-7免疫反应性呈剂量依赖性增加。在MCAO后第7天至第14天，接受BMP-7治疗的动物也表现出身体不对称的减少，第14天的运动活动增加。结论：我们的数据表明，脑卒中后经肠外注射BMP-7可以通过缺血侧血脑屏障，并在较长时间内诱导脑卒中动物的行为恢复。
Background and Purpose-We and others have previously reported that bone morphogenetic protein-7 (BMP-7), given before middle cerebral artery occlusion (MCAO), reduces ischemic injury in brain. Recent studies have indicated that receptors for BMP are upregulated after brain ischemia. It is possible that this upregulation may facilitate endogenous neurorepair in the ischemic brain. The purpose of this study was to determine the neuroregenerative effects of BMP-7 given parenterally after ischemia/reperfusion injury.Methods-Adult Sprague-Dawley rats were anesthetized with chloral hydrate. The middle cerebral artery was transiently occluded by a filament inserted through the right internal carotid artery. The filament was removed after 60-minute ischemia to allow reperfusion. Some animals were killed 24 hours after MCAO to examine BMP-7 mRNA expression. Other animals received a single dose of intravenous BMP-7 or vehicle at 24 hours after MCAO and were used for subsequent behavioral studies and BMP-7 immunostaining.Results-BMP-7 mRNA was upregulated 24 hours after MCAO in untreated animals. BMP-7 immunoreactivity was dose-dependently increased on the ischemic side of the hippocampus/dentate on day 6 after MCAO in animals receiving intravenous injection of BMP-7. Animals receiving BMP-7 also showed a decrease in body asymmetry from day 7 to day 14 and an increase in locomotor activity on day 14 after MCAO.Conclusions-Our data indicate that BMP-7, given parenterally after stroke, can pass through the blood-brain barrier on the ischemic side and induce behavioral recovery in stroke animals at longer testing times.