1992 Fiscal Year Final Research Report Summary
Molecular mechanism of "ischemic tolerance" phenomenon detected in neuronal cells of the brain
| Project/Area Number |
03670450
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
MATSUMOTO Masayasu Osaka University, Medical School, Assistant Professor, 医学部, 助手 (20192346)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Satoshi Osaka University, Medical School, Medical Staff, 医学部附属病院, 医員
WANAKA Akio Osaka University, Medical School, Associate Professor, 医学部, 講師 (90210989)
UEDA Hirokazu Osaka University, Medical School, Medical Staff, 医学部附属病院, 医員
HANDA Nobuo Osaka University, Medical School, Assistant Professor, 医学部, 助手 (80228676)
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| Project Period (FY) |
1991 – 1992
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| Keywords | garbil / cerebral ischemia / ischemic tolerance / stress protein / free radical / somatostatin / blood-brain barrier / apoptosis |
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| Research Abstract |
In the present study, we attempted to investigate the molecular mechanism of "ischemic tolerance" phenomenon detected in the hippocampal CA1 neurons of the gerbil brain. Through research works from 1991 to 1992, we could obtain the following results: 1. The neuronal cells in the various brain regions other than the hippocampus were proved to show "ischemic tolerance" phenomenon. 2. Prolonged but mild hypoperfusion could also induce "ischemic tolerance" phenomenon in gerbil hippocampal neurons. 3. Other than ischemic stress, preceding sublethal environmental stresses such as heat shock and oxidative stress could also induce tolerance of hippocampal neurons to forthcoming lethal ischemic stress. In these studies, the close relationships between the induction of tolerance phenomenon and induction of Mn superoxide dismutase and stress proteins such as heat shock protein 72.4. By immunostaing for synapsin I, microtubule-associated protein 2 and albumin, we could clearly detect the resynapto
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genesis in the contralateral dentate gyrus of the gerbils with unilateral hemispheric ischemia and the delayed blood-brain barrier opening following delayed neuronal death of the hippocampal CA1 neurons of the gerbils with transient forebrain ischemia. 5. By using in situ hybridization technique for somatostatin mRNA, we could show that hilar somatostatin neurons are more vulnerable to an ischemic insult than CA1 pyramidal neurons and sublethal ischemia, which can induce "ischemic tolerance" in the CA1 neurons, can cause death in the hilar somatostatin neurons. 6. We could also detect a characteristic ladder-like nucleosomal fragmentation of DNA, a specific biochemical marker of apoptosis in the hippocampus of the gerbils with 5 min forebrain ischemia and more than 54 hour reciruculation. These results suggested that several stress proteins including heat shock proteins induced by preceding sublethal ischemic insult play a crucial role for preventing apoptotic process or other detrimental processes triggered by lethal ischemic stress and the response of other types of cells than vulnerable neurons to ischemic stress should also be investigated for a full understanding of the molecular mechanism of a curious "ischemic tolerance" phenomenon of the neuronal cells of the brain. Less
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