Neuroregenerative effect of Bmp-7 In Stroke Animals

中风和相关的血管事件会对中枢神经系统(CNS)造成广泛的损害，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的程度，并在损伤后恢复受损的神经元。我们先前已经测试了骨形态发生蛋白-7(BMP-7)在局灶性脑缺血损伤中的作用。骨形态发生蛋白-7是生长因子B超家族中的一员。我们发现BMP-7在脑室给药后具有深刻的神经保护作用。本研究旨在探讨骨形态发生蛋白7在脑缺血再灌注损伤后的神经再生作用。成年SD大鼠用水合氯醛麻醉。用10-O线短暂结扎右侧大脑中动脉(MCA)1h。大脑中动脉闭塞后1d，向对侧脑室注入赋形剂或骨形态发生蛋白7。在大脑中动脉闭塞后第4天和第5天系统注射溴脱氧尿嘧啶(BrdU)，以确定可能的神经发生。接受BMP7治疗的动物显示出身体不对称和神经缺陷的快速纠正，这表明BMP7有助于中风后的恢复。在卒中后1个月处死动物，并用免疫组织学技术分析脑组织。BMP7治疗可增强BrdU在脑室下区、损毁皮质和穹隆体内的免疫反应。这些BrdU阳性细胞与Nestin和Neun共同标记。我们的行为学和解剖学数据表明，BMP7促进了中风动物的神经再生，可能是通过缺血后新的神经元前体的增殖。

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.