1996 Fiscal Year Final Research Report Summary
NEUROPROTECTION BY INDUCTION OF MN-SOD WITH DDS OR TRANSFECTION
| Project/Area Number |
07671551
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | KINKI UNIVERSITY |
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Principal Investigator |
AKAI Fumiharu KINKI UNV.NEURSERG,ASS.PROF., 医学部, 講師 (40122006)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGUTI Naoyuki OSAKA UNV., BIOPHIS., PROF, 医学部・生化学, 教授 (90002188)
KAETU Akira KINKI UNV.SCI.TEC., PROF., 理工学部, 教授 (00214247)
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| Project Period (FY) |
1995 – 1996
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| Keywords | ISCHEMIA / SOD / INDUCTION / ANIMAL MODEL / DDS / 梗塞モデル |
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| Research Abstract |
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
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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 Apoptosis was induced by administration of DDC in other malignant cell lines like malignant melanoma cells (unpublished DATA).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
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