Antithrombin reduces the ischemia/reperfusion-induced spinal cord injury in rats by attenuating inflammatory responses

Koji Hirose; Kenji Okajima; Yuji Taoka; Mitsuhiro Uchiba; Kan-yu Nakano; Junichi Utoh; Nobuo Kitamura

doi:10.1160/TH03-06-0385

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2004; 91(01): 162-170
DOI: 10.1160/TH03-06-0385

Cell Signalling and Vessel Remodelling

Schattauer GmbH

Antithrombin reduces the ischemia/reperfusion-induced spinal cord injury in rats by attenuating inflammatory responses

Autor*innen

Koji Hirose

¹Departments of Surgery and Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
Kenji Okajima

¹Departments of Surgery and Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
Yuji Taoka

¹Departments of Surgery and Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
Mitsuhiro Uchiba

¹Departments of Surgery and Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
Kan-yu Nakano

¹Departments of Surgery and Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
Junichi Utoh

¹Departments of Surgery and Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
Nobuo Kitamura

¹Departments of Surgery and Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan

Abstract

Summary

Antithrombin (AT) reveals its antiinflammatory activity by promoting endothelial release of prostacyclin (PGI₂) in vivo. Since neuroinflammation is critically involved in the development of ischemia/reperfusion (I/R)-induced spinal cord injury (SCI), it is possible that AT reduces the I/R-induced SCI by attenuating the inflammatory responses. We examined this possibility using rat model of I/R-induced SCI in the present study. AT significantly reduced the mortality and motor disturbances by inhibiting reduction of the number of motor neurons in animals subjected to SCI. Microinfarctions of the spinal cord seen after reperfusion were markedly reduced by AT. AT significantly enhanced the I/R-induced increases in spinal cord tissue levels of 6-keto-PGF_1α, a stable metabolite of PGI₂. AT significantly inhibited the I/R-induced increases in spinal cord tissue levels of TNF-α, rat interleukin-8 and myeloperoxidase. In contrast,Trp⁴⁹-modified AT did not show any protective effects. Pretreatment with indomethacin significantly reversed the protective effects of AT.An inactive derivative of factor Xa, which selectively inhibits thrombin generation, has been shown to fail to reduce SCI.Taken together, these observations strongly suggested that AT might reduce I/R-induced SCI mainly by the antiinflammatory effect through promotion of endothelial production of PGI₂. These findings also suggested that AT might be a potential neuroprotective agent.

Keywords

Antithrombin - ischemia/reperfusion - spinal cord injury - tumor necrosis factor-α - prostacyclin

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Referenzen

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