Neuroregenerative effect of Bmp-7 In Stroke Animals

Bmp-7 对中风动物的神经再生作用

• 批准号: 7149306
• 负责人: Yun Wang
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7149306
• 关键词: artery occlusion; bone morphogenetic proteins; bromodeoxyuridine; cerebral artery; cerebrovascular occlusions; corpus callosums; laboratory rat; nervous system regeneration; neuroprotectants; nonhuman therapy evaluation; stroke therapy

Stroke and related vascular events can cause widespread damage to the central nervous system (CNS) and result in significant motor and cognitive impairments. It has been suggested that trophic factor treatment may reduce the extent of damage and restore damaged neurons following the injury. We have previously tested the effects of bone morphogenetic protein-7 (BMP-7), a member of the transforming growth factor-B superfamily of growth factors, in focal brain ischemic injury. We found BMP-7 to have profound neuroprotective effects after intraventricular administration. 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 one hour. 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 4th and 5th 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 one 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.

中风和相关血管事件可导致中枢神经系统（CNS）的广泛损伤，并导致严重的运动和认知障碍。有人认为，营养因子治疗可以减轻损伤程度并恢复损伤后受损的神经元。我们先前已经测试了骨形态发生蛋白-7（BMP-7），生长因子的转化生长因子-B超家族的成员，在局灶性脑缺血损伤中的作用。我们发现BMP-7在脑室内给药后具有深刻的神经保护作用。本研究的目的是检查缺血/再灌注损伤后BMP 7的神经再生作用。用水合氯醛麻醉成年Sprague-Dawley大鼠。用10-O缝线短暂结扎右侧大脑中动脉（MCA）1小时。在MCA闭塞后一天，将媒介物或BMP 7输注到对侧脑室。为了确定可能的神经发生，在MCA闭塞后第4和第5天全身注射溴脱氧尿苷（BrdU）。用BMP 7治疗的动物显示出身体不对称和神经缺陷的快速纠正，表明BMP 7促进中风后的恢复。中风后一个月处死动物，并使用免疫组织学技术分析大脑。BMP 7处理增强了室管膜下区、受损皮质和胼胝体中BrdU的免疫反应性。这些BrdU阳性细胞与Nestin和NeuN共标记。我们的行为和解剖学数据表明，BMP 7促进中风动物的神经再生，可能是通过缺血后新的神经元前体细胞的增殖。