EXPRESSION OF BCL-2 FROM A DEFECTIVE HERPES-SIMPLEX VIRUS-1 VECTOR LIMITS NEURONAL DEATH IN FOCAL CEREBRAL-ISCHEMIA
EXPRESSION OF BCL-2 FROM A DEFECTIVE HERPES-SIMPLEX VIRUS-1 VECTOR LIMITS NEURONAL DEATH IN FOCAL CEREBRAL-ISCHEMIA
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DOI：
10.1161/01.str.26.9.1670
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发表时间：
1995-09-01
期刊：
影响因子：
8.3
通讯作者：
FEDEROFF, HJ
中科院分区：
文献类型：
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作者：
LINNIK, MD;ZAHOS, P;FEDEROFF, HJ
背景和目的在几种中风模型中，类似程序性细胞死亡的过程似乎有助于缺血后神经元的丢失。由于bcl-2基因的表达已被证明可以拯救神经元免于由于其他原因引起的程序性细胞死亡，方法复制缺陷型疱疹病毒载体（HSVbcl 2）或大肠杆菌lacZ（HSVlac），在通过串联永久性阻塞右侧大脑中动脉诱导新皮质局灶性缺血之前24小时，将同侧颈总动脉结果注射HSVbcl-2表达载体的动物，脑组织中bcl-2表达阳性，脑缺血24 h后，脑组织中bcl-2表达阳性。在注射HSVbcl 2的动物中，注射部位的活组织显著增加，但注射HSVlac的动物则没有。在HSV bcl 2动物中观察到的保护被定位到注射sites.Conclusions这些数据表明，bcl-2的表达保护神经元在体内缺血性损伤，并建议基因治疗中风和其他神经系统疾病，其中程序性细胞死亡参与的可行性。
Background and Purpose 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.Methods Replication 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.Results 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.Conclusions 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.