Fetal Kidney Tissue Transplantation And Bmp-7-induced Ne

骨形态发生蛋白-7（BMP-7）和胶质细胞源性神经营养因子（GDNF）均可减轻大鼠缺血性脑损伤。脑内移植胎肾组织，其中BMP-7和GDNF在发育过程中发挥重要作用，减少大脑皮质缺血性损伤。在这项研究中，我们测试了BMP-7参与这种神经保护反应的假设。将胎肾组织切成小块并移植到麻醉成年Sprague-Dawley大鼠右侧大脑中动脉（MCA）分布附近的皮质区域。原位杂交研究表明，这些胎肾移植后3天含有高水平的BMP-7 mRNA。在脑室内施用（ICV）BMP-7拮抗剂头蛋白（1 mg）后或在ICV媒介物后，对一些动物移植胎肾组织。右侧MCA随后短暂结扎60 min。接受胎肾组织移植的动物与未接受移植或接受胎肾移植和头蛋白预处理的卒中动物相比，身体不对称性明显降低。随后处死动物，取出脑用于氯化三苯基四唑染色。我们发现移植胎肾组织可以减少大脑皮层的梗死体积。Noggin预处理降低了胎肾移植诱导的保护作用。在缺血后8小时处死一组动物用于测定半胱天冬酶-3酶活性。胎肾移植显著降低缺血诱导的caspase-3活性。这种减少也可能会被诺金所对抗。总之，我们的数据表明，胎肾移植减少了成年大鼠缺血/再灌注诱导的皮质梗死和行为缺陷，这至少部分是通过移植物中BMP-7的作用介导的。

Both bone morphogenetic protein-7 (BMP-7) and glial cell line derived neurotrophic factor (GDNF) reduce ischemia-induced cerebral injury in rats. Intracerebral transplantation of fetal kidney tissue, in which BMP-7 and GDNF play important roles during development, reduced ischemic injury in cerebral cortex. In this study, we tested the hypothesis that BMP-7 is involved in this neuroprotective response. Fetal kidney tissues were cut into small pieces and transplanted into cortical areas adjacent to the right middle cerebral artery (MCA) distribution in anesthetized adult Sprague-Dawley rats. In situ hybridization study indicates that these fetal kidney transplants contained high levels of BMP-7 mRNA 3 days after grafting. Some animals were grafted with fetal kidney tissues after intraventricular administration (ICV) of the BMP-7 antagonist noggin (1 mg) or after ICV vehicle. The right MCA was later transiently ligated for 60 min. Animals receiving fetal kidney tissue transplantation developed significantly less body asymmetry, as compared to stroke animals that received no transplantation, or that received fetal kidney grafts and noggin pretreatment. Animals were later sacrificed and brains were removed for triphenyltetrazolium chloride staining. We found that transplantation of fetal kidney tissue reduced the volume of infarction in the cerebral cortex. Noggin pretreatment reduced the protection induced by fetal kidney grafting. A subgroup of animals were sacrificed 8 hours after ischemia for assay of caspase-3 enzymatic activity. Fetal kidney grafts significantly reduced ischemia-induced caspase-3 activity. This reduction could also be antagonized by noggin. In conclusion, our data suggest that fetal kidney transplantation reduces ischemia/reperfusion -induced cortical infarction and behavioral deficits in adult rats, which are, at least partially, mediated through the effect of BMP-7 in the transplants.