Adenovirus-mediated gene transfer of glial cell line-derived neurotrophic factor prevents ischemic brain injury after transient middle cerebral artery occlusion in rats
Adenovirus-mediated gene transfer of glial cell line-derived neurotrophic factor prevents ischemic brain injury after transient middle cerebral artery occlusion in rats
复制标题
DOI：
10.1097/00004647-199912000-00007
复制
发表时间：
1999-12-01
影响因子：
6.3
通讯作者：
Abe, K
中科院分区：
文献类型：
--
作者：
Kitagawa, H;Sasaki, C;Abe, K
为探讨外源性胶质细胞源性神经营养因子（glial cell line-derived neurotrophic factor，GDNF）基因表达对缺血性脑损伤的保护作用，在大鼠短暂性大脑中动脉闭塞（MCAO）前1天，将携带GDNF基因的复制缺陷型腺病毒载体（Ad-GDNF）直接注射到大脑皮层。2，3，5-三苯基四氮唑氯化物染色显示，在短暂MCAO后24小时，Ad-GDNF注射组的梗死体积显著小于赋形剂或Ad-LacZ治疗组。酶联免疫吸附试验（ELISA）检测GDNF的表达，结果显示，在短暂性脑缺血后24 h，Ad-GDNF组GDNF基因产物的表达明显高于对照组。Ad-GDNF组在MCAO前或MCAO后14 h，针道周围皮质GDNF免疫反应阳性染色明显，而溶媒组GDNF免疫反应阴性或弱阳性染色。Ad-GDNF组在短暂MCAO后24小时在同侧大脑皮层诱导的TUNEL、免疫反应性caspase-3和细胞色素c阳性神经元的数量显著减少。这些结果表明，成功的外源性GDNF基因转移改善缺血性脑损伤后短暂MCAO与凋亡信号的减少。
To examine a possible protective effect of exogenous glial cell line-derived neurotrophic factor (GDNF) gene expression against ischemic brain injury, a replication-defective adenoviral vector containing GDNF gene (Ad- GDNF) was directly injected into the cerebral cortex at 1 day before 90 minutes of transient middle cerebral artery occlusion (MCAO) in rats. 2,3,5-Triphenyltetrazolium chloride staining showed that infarct volume of the Ad-GDNF-injected group at 24 hours after the transient MCAO was significantly smaller than that of vehicle- or Ad-LacZ-treated group. Enzyme-linked immunosorbent assay (ELISA) for immunoreactive GDNF demonstrated that GDNF gene products in the Ad-GDNF-injected group were higher than those of vehicle-treated group at 24 hours after transient MCAO. Immunoreactive GDNF staining was obviously detected in the cortex around the needle track just before or 14 hours after MCAO in the Ad-GDNF group, whereas no or slight GDNF staining was detected in the vehicle group. The numbers of TUNEL, immunoreactive caspase-3, and cytochrome c-positive neurons induced in the ipsilateral cerebral cortex at 24 hours after transient MCAO were markedly reduced by the Ad-GDNF group. These results suggest that the successful exogenous GDNF gene transfer ameliorates ischemic brain injury after transient MCAO in association with the reduction of apoptotic signals.