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引起中枢神经系统（CNS）的广泛损伤，并导致严重的运动和认知障碍。有研究表明，营养因子治疗可以减轻损伤程度，恢复损伤后的神经元。我们之前已经测试了骨形态发生蛋白-7 （BMP-7）在局灶性脑缺血损伤中的作用，BMP-7是生长因子转化因子- b超家族的一员。我们发现脑室内给药后BMP-7具有深远的神经保护作用。本研究的目的是研究BMP7在缺血/再灌注损伤后的神经再生作用。用水合氯醛麻醉成年sd大鼠。用10-O线短暂结扎右侧大脑中动脉1小时。MCA闭塞1天后，向对侧脑室注入载体或BMP7。为了确定可能的神经发生，在MCA闭塞后第4天和第5天全身注射溴脱氧尿嘧啶（BrdU）。用BMP7治疗的动物显示出身体不对称和神经功能缺陷的快速纠正，这表明BMP7有助于中风后的恢复。动物在中风后一个月被处死，用免疫组织学技术分析大脑。BMP7治疗增强了BrdU在脑室下区、受损皮层和胼胝体的免疫反应性。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，BMP7促进中风动物的神经再生，可能是通过缺血后新神经元前体的增殖。