Role of neurotrophic factor for cerebral ischemia

神经营养因子在脑缺血中的作用

• 批准号: 09671426
• 负责人: KUMON Yoshiaki
• 金额: $ 1.22万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671426/
• 关键词: cerebral ischemia; neurotrophic factor; growth associated protein-43; water maze test; thalamus; ciliary neurotrophic factor; regeneration; 脳虚血; 神経栄養因子; 脳高次機能; 神経再生; 毛様体神経栄養因子; 視床

We evaluated the mechanism and the effect of neurotrophic factor on neuronal death in the ipsilateral thalamus following cortical infarction using the focal isehemia model of stroke-prone spontaneously hypertensive rats.(I) Slowly' progressive neuronal death which showed accumulation of calcium and decreased protein synthesis 3 and 5 days after ischemia was observed in the ipsilateral thalamus. This change was prevented by intraventricular administration of a protein synthesis inhibitor. The mechanism of neuronal death was considered to be apoptosis. (2) Growth-associated protein (GAP)-43, which is ta marker of the regenerated axons, was recognized 3 days after ischemia in the ipsilateral thalamus, and the axons from the spinal trigeminal nucleus or medial fascicular fibers were considered to be GAP-43 positive structures. These axons were decreased in number following ciliary neurotrophic factor (CNTF) intraventricular continuous administration. (3) Following CNTF iniraventricular administration during 4 weeks after isehemia, neuronal death in the ipsilateral thalamus as well as cortical infarction were prevented. Furthermore, the spatial learning ability studied by the Morris water maze test was preserved 2 and 4 weeks after isehemia.In conclusion, the neurotrophic factor prevented neurorial death in the ipsilateral thalanius, and preserved the spatial learning ability following focal cerebral isehemia.

我们利用脑卒中易发性高血压大鼠局灶性缺血模型，评估了神经营养因子对皮质梗死后同侧丘脑神经元死亡的机制和影响。（一）缓慢进行性神经元死亡，表现为钙积累和蛋白质合成减少。 3天和5天后在同侧丘脑中观察到缺血。通过心室内施用蛋白质合成抑制剂可以防止这种变化。神经元死亡的机制被认为是细胞凋亡。 (2) 生长相关蛋白(GAP)-43，是再生轴突的标记，在同侧丘脑缺血3天后被识别，来自脊髓三叉神经核或内侧束状纤维的轴突被认为是GAP -43正结构。心室内连续施用睫状神经营养因子（CNTF）后，这些轴突的数量减少。 (3)缺血后4周脑室内给予CNTF后，同侧丘脑神经元死亡以及皮质梗塞得到预防。此外，通过Morris水迷宫测试研究的空间学习能力在缺血后2周和4周得以保留。 总之，神经营养因子可以防止同侧丘脑的神经细胞死亡，并在局灶性脑缺血后保留空间学习能力。

项目成果

Watanabe H.,Kumon Y.,et al.: "Changes in protein synthesis and calcium homeostasis in the thalamus of spontaneously hypertensive rats with focal cerebral ischemia" Journal of Cerebral Blood Flow and Metabolism. 18. 686-696 (1998)

Watanabe H.，Kumon Y.，等人：“局灶性脑缺血自发性高血压大鼠丘脑中蛋白质合成和钙稳态的变化”脑血流和代谢杂志。

Watanabe H., Kumon Y., et al.: "Protein synthesis inhibitor transiently reduces neuronal death in the thalamus of spontaneously hypertensive rats following cortical infarction." Neuroscience Letters. 233. 25-28 (1997)

Watanabe H.、Kumon Y. 等人：“蛋白质合成抑制剂可暂时减少皮质梗塞后自发性高血压大鼠丘脑中的神经元死亡。”

Kumon Y., et al.: "Transient increase in the expression of growth-associated protein-43 in the thalamus of spontaneously hypertensive rats with cortical infarction." Biomedical Research. (in press). (1999)

Kumon Y. 等人：“患有皮质梗塞的自发性高血压大鼠的丘脑中生长相关蛋白 43 的表达短暂增加。”