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(Stroke. 2008;39:1883.)
© 2008 American Heart Association, Inc.

Original Contributions

Ubiquitin-Mediated Stress Response in the Spinal Cord After Transient Ischemia

Takashi Yamauchi, MD, PhD; Masahiro Sakurai, MD, PhD; Koji Abe, MD, PhD; Goro Matsumiya, MD, PhD Yoshiki Sawa, MD, PhD

From the Department of Cardiovascular Surgery (T.Y., G.M., Y.S.), Osaka University Graduate School of Medicine, Osaka, Japan; the Department of Cardiovascular Surgery (M.S.), National Hospital Organization Sendai Medical Center, Sendai, Japan; and the Department of Neurology (K.A.), Okayama University Graduate School of Medicine, Okayama, Japan.

Correspondence to Takashi Yamauchi, MD, PhD, Department of Cardiovascular Surgery, Osaka University Graduate school of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. E-mail yamataka{at}surg1.med.osaka-u.ac.jp

Background and Purpose— Vulnerability of motor neurons in the spinal cord against ischemia is considered to play an important role in the development of delayed paraplegia after surgery of the thoracic aorta. However, the reasons for such vulnerability are not fully understood. Recently, the ubiquitin system has been reported to participate in neuronal cell death. In the present study, we investigated the expression of ubiquitin system molecules and discussed the relationship between the vulnerability and the ubiquitin system after transient ischemia in the spinal cord.

Methods— Fifteen minutes of spinal cord ischemia in rabbits was applied with the use of a balloon catheter. In this model, the spinal motor neuron shows selectively delayed neuronal death, whereas other spinal neurons such as interneurons survive. Immunohistochemical analysis and Western blotting for ubiquitin system molecules, ubiquitin, deubiquitylating enzyme (ubiquitin carboxy-terminal hydrolase 1), and ubiquitin-ligase parkin were examined.

Results— In cytoplasm, ubiquitin and ubiquitin carboxy-terminal hydrolase 1were strongly induced both in interneuron and motor neuron at the early stage of reperfusion, but the sustained expression was observed only in motor neuron. Parkin was induced strongly at 3 hours after the reperfusion, but the immunoreactivity returned to the sham control level at 6 hours in both neurons. In the nuclei, ubiquitin, ubiquitin carboxy-terminal hydrolase 1, and parkin were strongly induced in interneuron, whereas no upregulation of these proteins was observed in motor neuron.

Conclusions— These results indicate that the vulnerability of motor neuron of the spinal cord might be partially attributed to the different response in ubiquitin-mediated stress response after transient ischemia.

Key Words: ischemia • paraplegia • parkin • spinal cord ischemia • ubiquitin • UCH-L1