| Project/Area Number |
06454433
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | The University of Tokushima |
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Principal Investigator |
IKATA Takaaki The University of Tokushima, School of Medicine, professor, 医学部, 教授 (80108860)
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| Co-Investigator(Kenkyū-buntansha) |
KATOH Shinsuke The University of Tokushima, School of Medicine, Lecturer, 医学部, 講師 (30243687)
FUKUZAWA Kenji The University of Tokushima, Faculty of pharmaceutical Sciences, Professor, 薬学部, 教授 (90035551)
FUKUI Yoshihiro The University of Tokushima, School of Medicine, professor, 医学部, 教授 (50144168)
OKA Motoo The University of Tokushima, School of Medicine, professor, 医学部, 教授 (60028298)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Spinal cord / Trauma / Oxidative stress / Eicosanoids / Vitamin C / Nitric oxide / Intercellular adhesion molecule-1 / 脊髄損傷 / 過酸化脂質 |
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| Research Abstract |
We investigated roles of oxidative stress and nitric oxide (NO) in the spinal cord after compression injury to investigate the modality to minimize cord damage after spinal cord trauma. Our study demonstrated that tromboxane A_2, prostaglandin I_2 and leucotriene C_4 are involved in the secondary pathological changes and inhibition of these eicosanoids can prevent the damage partially. We also demonstrated the protective effect of vitamin C as a scavenger of water soluble free radicals, and that its effect is not synergistic with that of vitamin E.
Activated neutrophil is one of major sources of oxidative stress. We demonstrated the expression of the intercellular adhesion molecule 1 (ICAM-1) which promotes its infiltration to the spinal cord after injury, and that passive immunization of ICAM-1 enhances neurological recovery.
Nitric oxide (NO) has been proposed to have neurotoxic and neuroprotective. We showed the increase of NO after spinal cord injury (SCI). Expression of mRNA of constitutive NO synthase (c-NOS) was not changed, however, that of inducible NOS (i-NOS) increased within 7 days of injury. Inhibition of c-NOS worsened and that of i-NOS improved motor function after SCI.These results indicate that NO induced by i-NOS may be neurotoxic in the sub-acute phase after SCI.Down-regulation of i-NOS mRNA by transforming growth factor-beta1 (TGF-beta1) was also demonstrated after SCI.Although early recovery of motor dysfunction was promoted by TGF-beta1 treatment, however, final motor function was not better because of increase of fibrous scar formation in the injured spinal cord.
These results indicate that oxidative stress through arachidonate cascade or activated neutrophil, and NO play important roles in the secondary pathological changes after mechanical injury to the spinal cord. From the time course after SCI,ICAM-1 and i-NOS can be targets of pharmacological treatment to prevent further degeneration after spinal cord injuries.
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