1997 Fiscal Year Final Research Report Summary
Activated protein C reduces the severity of compression-induced spinal cord injury in rats by inhibiting cytokine production
| Project/Area Number |
08671242
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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 |
Hematology
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| Research Institution | Kumamoto University |
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Principal Investigator |
OKAJIMA Kenji Kumamoto University School of Medicine, Department of Laboratory Medicine, Associate Professor, 医学部, 助教授 (60152295)
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| Project Period (FY) |
1996 – 1997
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| Keywords | activated protein C / post-traumatic spinal cord injury / leukocytes / motor disturbances / TNF-alpha / neutrophils |
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| Research Abstract |
Activated protein C (APC), an important inhibitor of the coagulation system, has recently been shown to prevent tissue injury by blocking the activation of leukocytes. To determine whether APC can also prevent post-traumatic spinal cord injury (SCI), a condition in which leukocytes play an important role, we tested the effects of APC on SCI induced in rats by compression trauma. Administration of APC,either before or after the induction of SCI,markedly reduced the motor disturbances in these animals. In contrast, neither an inactive derivative of activated factor X (DEGR-Xa), a selective inhibitor of thrombin generation, nor active site-blocked APC (DIP-APC) reduced the motor disturbances. Histologic examination revealed that intramedullary hemorrhages, observed 24 hours after trauma, were significantly reduced in the animals administered APC.The increase in the tissue level of tumor necrosis factor-a (TNF-a) and the accumulation of neutrophils in the damaged segment of the spinal cord were significantly inhibited in the animals that had received APC,but these were not inhibited in those administered with DIP-APC or DEGR-Xa. The induction of leukocytopenia had the same effect as APC,in that it significantly reduced motor disturbances, tissue levels of TNF-a, and neutrophil accumulation in the animals subjected to compressive SCI.These findings suggest that in SCI,APC reduces motor disturbances primarily by reducing the amount of TNF-a at the site of injury, thus inhibiting neutrophil accumulation and the resultant damage to the endothelial cells.
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Research Products
(14 results)
