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能对中枢神经系统（CNS）造成广泛损害，并导致严重的运动和认知障碍。有人建议，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。我们之前测试过骨形态发生蛋白 7 (BMP-7)（生长因子转化生长因子 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远的神经保护作用。本研究的目的是检查缺血/再灌注损伤后 BMP7 的神经再生作用。用水合氯醛麻醉成年斯普拉格-道利大鼠。用10-O缝线暂时结扎右大脑中动脉(MCA)一小时。 MCA 闭塞一天后，将媒介物或 BMP7 注入对侧脑室。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苷 (BrdU)。用 BMP7 治疗的动物表现出身体不对称和神经缺陷的快速纠正，表明 BMP7 有助于中风后的恢复。中风后一个月处死动物，并使用免疫组织学技术分析大脑。 BMP7 治疗增强了室下区、病变皮质和胼胝体中 BrdU 的免疫反应性。这些 BrdU 阳性细胞与巢蛋白和 NeuN 共同标记。我们的行为和解剖数据表明，BMP7 可能通过缺血后新神经元前体的增殖来促进中风动物的神经再生。