JTCS Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lu, K.
Right arrow Articles by Chen, H.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lu, K.
Right arrow Articles by Chen, H.-J.
Related Collections
Right arrow Great vessels
Right arrow Molecular biology

J Thorac Cardiovasc Surg 2007;133:934-941
© 2007 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Inhibition of the MEK/ERK pathway reduces microglial activation and interleukin-1-beta expression in spinal cord ischemia/reperfusion injury in rats

Kang Lu, MD, PhDa, Chung-Lung Cho, PhDb, Cheng-Loong Liang, MDa, Shang-Der Chen, MDc, Po-Chou Liliang, MDa, Shin-Yuan Wang, MSd, Han-Jung Chen, MD, PhDa,*

a Department of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
d Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
b Department of Biological Sciences, National Sun-Yat Sen University, Kaohsiung, Taiwan
c Department of Neurology, Chang-Gung Memorial Hospital, Kaohsiung, Taiwan.

Received for publication August 18, 2006; revisions received October 12, 2006; accepted for publication November 3, 2006.

* Address for reprints: Han-Jung Chen, MD, PhD, Department of Neurosurgery, E-Da Hospital, I-Shou University, 1 E-Da Road, Yan-Chau Shiang, Kaohsiung 824, Taiwan. (Email: chenmd{at}ms8.hinet.net).

Objectives: Ischemic spinal cord injury is a serious complication of aortic surgery. Although the extracellular signal-regulated kinases 1 and 2 are generally regarded as related to cell proliferation and survival, increasing evidence suggests that the role of the extracellular signal-regulated kinase pathway in ischemia/reperfusion injury is much more sophisticated.

Methods: Spinal cord ischemia in rats was induced by occluding the thoracic descending aorta with a balloon catheter introduced through a femoral artery, accompanied by concomitant exsanguination. Rats in the control group were given dimethyl sulfoxide (vehicle) before undergoing spinal cord ischemia/reperfusion injury. In the U0126-treated group, rats were pretreated with a specific inhibitor of the mitogen-activated protein kinase/extracellular signal-regulated kinases 1 and 2, U0126, to inhibit extracellular signal-regulated kinases 1 and 2 phosphorylation. The sham-operated rats underwent aortic catheterization without occlusion. Parameters, including neurologic performance, neuronal survival, inflammatory cell infiltration, and interleukin-1ß production in the spinal cords, were compared between groups.

Results: Early extracellular signal-regulated kinases 1 and 2 phosphorylation was observed after injury in the control group, followed by abundant microglial accumulation in the infarct area and increased interleukin-1ß expression. In the U0126 group, U0126 treatment completely blocked extracellular signal-regulated kinases 1 and 2 phosphorylation. Microglial activation and spinal cord interleukin-1ß levels were significantly reduced. Neuronal survival and functional performance were improved.

Conclusions: The mitogen-activated protein kinase/extracellular signal-regulated kinase pathway may play a noxious role in spinal cord ischemia/reperfusion injury by participating in inflammatory reactions and cytokine production. Targeting this pathway may be of potential value in terms of therapeutic intervention.

Abbreviations and Acronyms CBP = carotid blood pressure; CNS = central nervous system; ERK = extracellular signal-regulated kinase; GFAP = glial fibrillary acidic protein; IL = interleukin; I/R = ischemia/reperfusion; MAPK = mitogen-activated protein kinase; MEK = MAPK/ERK kinase; MPO = myeloperoxidase; p-ERK = phosphorylated extracellular signal-regulated kinase






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS
Copyright © 2007 by The American Association for Thoracic Surgery.