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(Stroke. 2005;36:1538.)
© 2005 American Heart Association, Inc.

Original Contributions

Role of c-Jun N-Terminal Kinase in Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage

Hiroshi Yatsushige, MD; Mitsuo Yamaguchi, MD; Changman Zhou, MD, PhD; John W. Calvert, BS John H. Zhang, MD, PhD

From the Department of Physiology (H.Y., M.Y., J.W.C., C.Z., J.H.Z.), Loma Linda University School of Medicine; the Division of Neurosurgery (J.H.Z.), Loma Linda University Medical Center, Loma Linda, Calif; the Department of Neurosurgery (H.Y., M.Y., J.W.C., J.H.Z.), Louisiana State University Health Science Center, Shreveport, La; and the Department of Neurosurgery (H.Y.), National Hospital Organization Disaster Medical Center and Section of Neurosurgery (H.Y.), Department of Brain Medical Science, Division of Cognitive and Behavioral Medicine, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.

Correspondence to John H. Zhang, MD, PhD, Division of Neurosurgery, Loma Linda University Medical Center, 11234 Anderson Street, Room 2562B, Loma Linda, CA 92354. E-mail johnzhang3910{at}yahoo.com

Background and Purpose— Inflammation could play a role in cerebral vasospasm after subarachnoid hemorrhage (SAH). SP600125 a c-Jun N-terminal kinase (JNK) inhibitor reduces inflammation. The present study examined if SP600125 could reduce cerebral vasospasm.

Methods— Twenty-seven dogs were assigned to 5 groups: control, SAH, SAH plus dimethyl sulfoxide (DMSO), SAH plus SP600125 (10 µmol/L), and SAH plus SP600125 (30 µmol/L). SAH was induced by the injection of autologous blood into the cisterna magna on day 0 and day 2. Angiograms were evaluated on day 0 and day 7. The behavior of the dogs was evaluated daily. The activation of the JNK pathway, the infiltration of leukocytes, and the production of cytokines were also evaluated.

Results— Severe vasospasm was observed in the basilar artery of SAH and DMSO dogs. The JNK signaling pathway was activated in the basilar artery after SAH and SP600125 reduced angiographic and morphological vasospasm and improved behavior scores with a concomitant reduction of infiltrated leukocytes and IL-6 production.

Conclusions— These results demonstrate that SP600125 attenuated cerebral vasospasm through a suppressed inflammatory response, which may provide a novel therapeutic target for cerebral vasospasm.

Key Words: cerebral vasospasm • inflammation • JNK • subarachnoid hemorrhage

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