Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neurosciences Area of IdiPAZ, Health Research Institute, Autónoma University of Madrid, Madrid, Spain.
Neurochem Int. 2012 Feb;60(3):310-7. doi: 10.1016/j.neuint.2011.12.015. Epub 2011 Dec 30.
We investigated the effect of CDP-choline on brain plasticity markers expression in the acute phase of cerebral infarct in an experimental animal model. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (pMCAO) and treated or not with CDP-choline (500 mg/kg) daily for 14 days starting 30 min after pMCAO. Functional status was evaluated with Roger's test; lesion volume with magnetic resonance imaging (MRI) and hematoxylin and eosin staining (H&E); cell death with TUNEL; cellular proliferation with BrdU immunohistochemistry; vascular endothelial growth factor (VEGF), synaptophysin, glial fibrillary acidic protein (GFAP) and low-density lipoprotein receptor-related protein (LRP) by immunofluorescence and Western-blot techniques. CDP-choline significantly improved functional recovery and decreased lesion volume on MRI, TUNEL-positive cell number and LRP levels at 14 days. In addition, CDP-choline significantly increased BrdU, VEGF and synaptophysin values and decreased GFAP levels in the peri-infarct zone compared with the infarct group. In conclusion, our data indicate that CDP-choline improved functional recovery after permanent middle cerebral artery occlusion in association with reductions in lesion volume, cell death and LRP expression. In fact, CDP-choline increased cell proliferation, vasculogenesis and synaptophysin levels and reduced GFAP levels in the peri-infarct area of the ischemic stroke.
我们研究了胞磷胆碱对实验性脑梗死急性期脑可塑性标志物表达的影响。雄性 Sprague-Dawley 大鼠接受永久性大脑中动脉闭塞（pMCAO），并在 pMCAO 后 30 分钟开始每日接受胞磷胆碱（500mg/kg）治疗 14 天。功能状态通过 Roger 测试评估；损伤体积通过磁共振成像（MRI）和苏木精-伊红染色（H&E）评估；细胞死亡通过 TUNEL 检测；细胞增殖通过 BrdU 免疫组织化学检测；血管内皮生长因子（VEGF）、突触素、胶质纤维酸性蛋白（GFAP）和低密度脂蛋白受体相关蛋白（LRP）通过免疫荧光和 Western-blot 技术检测。胞磷胆碱显著改善了功能恢复，降低了 MRI 上的损伤体积、TUNEL 阳性细胞数量和 14 天时的 LRP 水平。此外，与梗死组相比，胞磷胆碱在梗死周围区显著增加了 BrdU、VEGF 和突触素的水平，并降低了 GFAP 的水平。总之，我们的数据表明，胞磷胆碱可改善永久性大脑中动脉闭塞后的功能恢复，同时降低损伤体积、细胞死亡和 LRP 表达。事实上，胞磷胆碱增加了缺血性卒中梗死周围区的细胞增殖、血管生成和突触素水平，并降低了 GFAP 水平。
