THE ROLE OF BRAIN-DERIVED NEUROTROPHIC FACTOR IN TRANSIENT FOREBRAIN ISCHEMIA IN THE RAT-BRAIN
THE ROLE OF BRAIN-DERIVED NEUROTROPHIC FACTOR IN TRANSIENT FOREBRAIN ISCHEMIA IN THE RAT-BRAIN
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DOI：
10.1227/00006123-199402000-00016
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发表时间：
1994-02-01
期刊：
影响因子：
4.8
通讯作者：
TANIGUCHI, T
中科院分区：
文献类型：
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作者：
TSUKAHARA, T;YONEKAWA, Y;TANIGUCHI, T
脑源性神经营养因子（BDNF）可能在脑缺血后神经元细胞死亡的病理生理学中起作用。我们研究了大鼠短暂前脑缺血后BDNF基因表达的变化以及BDNF对神经元死亡的影响。通过阻断双侧颈总动脉和产生全身性低血压8分钟来诱导短暂性前脑缺血。用~（32）P标记的小鼠BDNF互补脱氧核糖核酸探针，通过北方印迹分析，检测海马和大脑皮质中BDNF信使核糖核酸含量的变化。用BDNF互补脱氧核糖核酸表达载体转染中国仓鼠卵巢细胞，建立了分泌BDNF的重组细胞。然后，通过连续脑室内输注200 μ l正常（组II，n = 6）或30倍浓缩的含有BDNF的重组中国仓鼠卵巢细胞培养基（组IV，n = 6），检测BDNF对缺血后海马CA 1区神经元死亡的影响。正常（组I，n = 6）或30倍浓缩（组III，n = 6）的中国仓鼠卵巢细胞培养基，不包括BDNF互补脱氧核糖核酸，注入相同的缺血脑，作为对照。北方印迹分析显示，两种不同长度的BDNF信使核糖核酸的量短暂性前脑缺血后，海马区BDNF信使核糖核酸（1.5Kb和4.2Kb）迅速升高，2 h达高峰，12 h恢复到正常水平，而大脑皮质区BDNF信使核糖核酸水平升高较慢，峰值出现在缺血后6小时。缺血7天后海马CA 1区的细胞死亡率为22% +/- 8%（平均值+/- SD，n = 6）; 27% +/- 8%组II中为22% ± 5%（平均值+/- SD，n = 6）;组III中为22% ± 5%（平均值+/- SD，n = 6）;组IV中为1% ± 1%（平均值+/- SD，n = 6）。这些结果表明，BDNF基因的表达增强短暂性缺血在海马和大脑皮层，BDNF，在足够的剂量，具有预防作用的迟发性海马神经元死亡后观察到短暂性前脑缺血。
BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) may play a role in the pathophysiology of neuronal cell death after cerebral ischemia. We investigated alterations in BDNF gene expression and the effect of BDNF on neuronal death after transient forebrain ischemia in the rat brain. Transient forebrain ischemia was induced by occlusion of the bilateral common carotid arteries and by producing systemic hypotension for 8 minutes. The alterations in the BDNF messenger ribonucleic acid content in the hippocampus and the cerebral cortex were examined by Northern blot analysis, using a phosphorus-32-labeled mouse BDNF complementary deoxyribonucleic acid probe. Recombinant Chinese hamster ovary cells with BDNF-secreting capacity were established by expression vector transfection with BDNF complementary deoxyribonucleic acid. The effect of BDNF on neuronal death in the hippocampal CA1 region after ischemia was then examined by using a continuous intraventricular infusion of 200 mu l of normal (Group II, n = 6) or 30-times concentrated recombinant Chinese hamster ovary cell culture medium containing BDNF (Group IV, n = 6). Normal (Group I, n = 6) or 30-times concentrated (Group III, n = 6) Chinese hamster ovary cell culture medium, not including BDNF complementary deoxyribonucleic acid, was infused into the same ischemic brains, which served as controls. Northern blot analysis showed that the amounts of BDNF messenger ribonucleic acid of two different lengths (1.5 Kb and 4.2 Kb) in the hippocampus increased rapidly, reached a maximum in 2 hours, and returned to the normal level 12 hours after transient forebrain ischemia, whereas, in the cerebral cortex, the level of BDNF messenger ribonucleic acid increased more slowly, with the peak occurring 6 hours after the ischemia. Cell death in the hippocampal CA1 region 7 days after the ischemia was 22% +/- 8% (mean +/- SD, n = 6) of the total CA1 neurons in Group I; 27% +/- 8% (mean +/- SD, n = 6) in Group II; 22% +/- 5% (mean +/- SD, n = 6) in Group III; and 1% +/- 1% (mean +/- SD, n = 6) in Group IV. These results suggested that BDNF gene expression was enhanced by transient ischemia both in the hippocampus and in the cerebral cortex and that BDNF, at a sufficient dose, has a preventive effect on the delayed hippocampal neuronal death observed after transient forebrain ischemia.