| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
Thrombin is a member of serine protease family, and has been well known to have multifunctions in coagulation, inflammation, regulation of blood vessels and central nervous systems (CNS). While thrombin effects on the brain tissues in restoring from damage, it also causes the post brain damage through glial reaction and scar formation after injury.
In order to elucidate the effects of thrombin on the purpose of therapeutic application, we investigated the following studies by using anti-thrombin drug, named argatroban, in a rat brain injury model, histologically :
(1) Effect of thrombin on the inflammatory cells : infiltration and accumulation of inflammatory cells, especially around the small vessels through expressing the adhesion molecules on the endothelial cells, and
(2) Effects of thrombin on cells comprising central nervous system : glial response, especially, of the astrocytes when excess of thrombin or inhibitor for thrombin were administered in a rat brain injury model.
Result 1
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: Thrombin inhibitor suppressed the infiltration of inflammatory cells and excessive gliosis mainly composed of vimentin-positive astroglia, but not effected on the expression of GFAP-positive astrocytes along the injured area of rat brain.
Result 2 : Thrombin accelerated the infiltration of inflammatory cells and the expression of E-selectin and ICAM-1 on the endothelial cells along the edge of brain defect.
Result 3 : Thrombin inhibitor suppressed the infiltration of inflammatory cells and the expression of ICAM-1 on the endothelial cells, and also suppressed the accumulation of Mac-1 positive cell along the edge of brain defect.
Conclusion
Thrombin caused infiltration of inflammatory cells through the expression of adhesion molecules on the endothelial cells, and led to secondary brain damage after acute inflammation.
Thrombin accelerated proliferation of vimentin-positive astrocytes after brain injury.Thrombin inhibitor may minimize the secondary brain damage, and promote the neural regeneration. Less
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