NEUROPROTECTION BY INDUCTION OF MN-SOD WITH DDS OR TRANSFECTION

本研究的目的之一是通过控制释放细胞因子、生长因子和神经递质来诱导Mn-SOD。DDS与IL-1或TSH复合后，对Mn-SOD蛋白的诱导作用增强1.5 ~ 2倍，对缺血性损伤有保护作用，但在1 mm直径的小球周围出现了意外的创伤性变性。免疫组织化学染色显示邻近神经元凋亡，DNA内标显示。虽然我们未能证明细胞凋亡的变化与电子显微镜研究。这些结果迫使我们改变策略，使用连续立体定向显微注射（渗透泵，Alzet）。在体外培养的PC 12细胞中，DDC能螯合金属离子，使SOD活性降低，自由基相对含量增加。PC 12细胞有少量凋亡小体，但大多数细胞死亡为坏死。未观察到DNA片段化。SOD活性受到抑制，但自由基却没有受到抑制。 ...更多信息 不移位。在其他恶性细胞系（如恶性黑色素瘤细胞）中给予DDC可诱导细胞凋亡（未发表数据）。本研究得出了选择性脆弱性的结论。感觉神经元对放射性损伤具有耐受性。运动神经元细胞是下一步研究的靶点，建立了一种新的缺血模型并发表（Neuro Sci Lett，1996等）。5 μ m的铁粒子的电磁血栓形成在中枢神经系统的任何相关区域产生局灶性缺血。皮质梗死成功率为100%，其中60%为出血性。用新制备的抗DNA单链抗体证实细胞凋亡。p53的表达被证明在脆弱的神经元，如CA 1锥体细胞开始神经元死亡之前，也在神经胶质细胞之前，减少他们的数量。可以想象，神经胶质细胞也受到程序性细胞死亡机制的调节。采用电磁血栓法建立脊髓缺血模型。将磁功率控制在360 G，造成Wister大鼠脊髓背侧静脉梗塞，沙鼠脊髓前动脉闭塞。根据症状将动物分为5组（Neuropathol，1996）。少

One of the aim of this study was induction of Mn-SOD by controlled release of cytokines, growth factors and neurotrasmitters. DDS composite with IL1 or TSH caused 1.5 to two times induction of Mn-SOD protein and protection against ischemic injury, though unexpected traumatic degeneration around the pellet of 1mm diameter. Immunohistochemical study showed apoptosis of the adjacent neurons, demonstrated with DNA endolabeling. Although we failed to demonstrate apoptotic changes with electron microscopic study. Those results compelled to change our strategy, using continuous stereotactic microinjection (Osmotic pump, Alzet). In vitro culture study, PC12 cells were exposed to DDC,which chelates metal ions and then decreases the activity of SOD.Consequently relative amount of free radical increase. A few PC12 cells showed apoptotic bodies, but most of the cell death was rather necrosis. DNA fragmentation was not observed. And moreover activity of SOD was suppressed, though free radical was n … More ot shifted. Apoptosis was induced by administration of DDC in other malignant cell lines like malignant melanoma cells (unpublished DATA). Selective vulnerability was concluded in this study. Sensory neurons were tolerant to radical injury. Motor neuron cells should be targeted in the next study.A new ischemic model was established and published (Neuro Sci Lett, 1996, etc.). Electromagnetic thrombosis by 5mum of iron particles created focal ischemia in any concerned area of the central nervous system. Cortical infarctions were successfully made at 100% and 60% of them were hemorrhagic. Apoptosis was confirmed by a newly made antibody against DNA-single-strand. Expression of p53 was demonstrated in the vulnerable neurons like as CA1 pyramidal cells before starting neuronal death and also in the glial cells prior to diminishing their number. It is conceivable that glial cells are also regulated by the mechanism of program cell death. Electromagnetic thrombosis model was applied for spinal cord ischemia. Controlling the magnetic power at 360G,venous infarction of dorsal spinal cord was made in Wister rat and anterior spinal artery occlusion was established in the spinal cord of gerbil. Animals were divided into 5 groups depend on the symptoms (Neuropathol, 1996). Less