Linnik M D, Zahos P, Geschwind M D, Federoff H J
Department of Neurosurgery, University of Cincinnati College of Medicine, Marion Merrell Dow Research Institute, Ohio, USA.
Stroke. 1995 Sep;26(9):1670-4; discussion 1675. doi: 10.1161/01.str.26.9.1670.
A process resembling programmed cell death appears to contribute to postischemic neuronal loss in several models of stroke. Because the expression of the bcl-2 gene has been shown to rescue neurons from programmed cell death due to other causes, we determined whether it would be similarly neuroprotective in stroke.
Replication of defective herpes viral vectors that transduce bcl-2 (HSVbcl2) or Escherichia coli lacZ (HSVlac) were injected into two sites in the rat cerebral cortex 24 hours before induction of neocortical focal ischemia by tandem permanent occlusion of the right middle cerebral artery and ipsilateral common carotid artery. Local ischemic damage was determined 24 hours after occlusion by staining with 2% 2,3,5-triphenyltetrazolium chloride.
Expression of bcl-2 in cerebral cortex was confirmed by immunohistochemistry in animals injected with the HSVbcl2 expression vector. Viable tissue was significantly increased at the injection sites in HSVbcl2- but not HSVlac-injected animals. The protection observed in the HSVbcl2 animals was localized to the injection sites.
These data indicate that bcl-2 expression protects neurons in vivo from ischemic injury and suggest the feasibility of gene therapy for stroke and perhaps other neurological diseases in which programmed cell death is involved.
在几种中风模型中，一种类似于程序性细胞死亡的过程似乎导致了缺血后神经元的丧失。由于已表明bcl - 2基因的表达可使神经元从其他原因导致的程序性细胞死亡中获救，我们确定它在中风中是否同样具有神经保护作用。
在通过右侧大脑中动脉和同侧颈总动脉串联永久性闭塞诱导新皮质局灶性缺血前24小时，将转导bcl - 2（HSVbcl2）或大肠杆菌β - 半乳糖苷酶（HSVlac）的缺陷型疱疹病毒载体注射到大鼠大脑皮质的两个部位。闭塞24小时后，用2%的2,3,5 - 氯化三苯基四氮唑染色来确定局部缺血损伤情况。
通过免疫组织化学在注射HSVbcl2表达载体的动物中证实了大脑皮质中bcl - 2的表达。在注射HSVbcl2而非HSVlac的动物中，注射部位的存活组织显著增加。在HSVbcl2动物中观察到的保护作用局限于注射部位。
这些数据表明bcl - 2的表达在体内可保护神经元免受缺血性损伤，并提示基因治疗中风以及可能其他涉及程序性细胞死亡的神经疾病的可行性。
