Lukkarinen J, Gröhn O H, Sinervirta R, Järvinen A, Kauppinen R A, Jänne J, Alhonen L I
Nuclear Magnetic Resonance Research Group, University of Kuopio, Finland.
Stroke. 1997 Mar;28(3):639-45. doi: 10.1161/01.str.28.3.639.
Cerebral ischemia causes activation of ornithine decarboxylase (ODC) gene and subsequent accumulation of putrescine, which might either directly or indirectly affect the outcome of cerebral infarct. We developed a transgenic rat overexpressing human ODC, which was used to explore the effect of abnormally high putrescine concentration in the brain on the infarct volume after permanent middle cerebral artery (MCA) occlusion.
The transgenic rats were produced by the pronuclear injection technique with the use of cloned human ODC gene. The right MCA was permanently occluded through craniotomy. ODC activity and polyamines were assayed in the infarcted and contralateral hemispheres. MRI was used to quantify T2 relaxation time, apparent diffusion constant (ADC), and infarct volume, which was also determined by 2,3,5-triphenyltetrazolium chloride.
Permanent MCA occlusion resulted in extensive activation of ODC, which was approximately sevenfold greater than in syngenic animals at 20 hours after occlusion. Consequently, putrescine increased from approximately 10 and 230 pmol/mg to 160 and 410 pmol/mg in the infarcted hemisphere of syngenic and transgenic animals, respectively, but all the other polyamines were unchanged. This high putrescine in the transgenic rats did not influence infarct size evolution, as determined by MRI, T2, ADC, or the infarct volume by 2,3,5-triphenyltetrazolium chloride at 48 hours.
Data from the ODC transgenic rat model show that the development of brain infarct after permanent MCA occlusion was not influenced by extensive levels of putrescine, indicating that this endogenous amine is not involved in maturation and spread of stroke lesion in vivo. Thus, it seems that ODC activation reflects an endogenous adaptation of neural cells to a noxious stimulus that does not directly influence lesion development.
脑缺血会导致鸟氨酸脱羧酶（ODC）基因激活以及随后腐胺的积累，这可能直接或间接影响脑梗死的结局。我们构建了一种过表达人ODC的转基因大鼠，用于探究脑中异常高浓度的腐胺对永久性大脑中动脉（MCA）闭塞后梗死体积的影响。
采用原核注射技术，利用克隆的人ODC基因培育转基因大鼠。通过开颅手术永久性闭塞右侧MCA。检测梗死侧和对侧半球的ODC活性及多胺。使用MRI定量T2弛豫时间、表观扩散常数（ADC）和梗死体积，同时也通过2,3,5-三苯基氯化四氮唑来测定梗死体积。
永久性MCA闭塞导致ODC广泛激活，在闭塞后20小时，其激活程度比同基因动物大约高7倍。因此，在同基因和转基因动物的梗死半球中，腐胺分别从约10和230 pmol/mg增加到160和410 pmol/mg，但所有其他多胺均未改变。通过MRI、T2、ADC或48小时时2,3,5-三苯基氯化四氮唑测定的梗死体积确定，转基因大鼠中这种高浓度腐胺并未影响梗死大小的演变。
来自ODC转基因大鼠模型的数据表明，永久性MCA闭塞后脑梗死的发展不受大量腐胺水平的影响，这表明这种内源性胺不参与体内中风病变的成熟和扩散。因此，ODC激活似乎反映了神经细胞对有害刺激的内源性适应，而这种适应并不直接影响病变的发展。
