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(Stroke. 2007;38:1354.)
© 2007 American Heart Association, Inc.

Original Contributions

Novel Protein Transduction Method by Using 11R

An Effective New Drug Delivery System for the Treatment of Cerebrovascular Diseases

Tomoyuki Ogawa, MD; Shigeki Ono, MD, PhD; Tomotsugu Ichikawa, MD, PhD; Seiji Arimitsu, MD; Keisuke Onoda, MD, PhD; Koji Tokunaga, MD, PhD; Kenji Sugiu, MD, PhD; Kazuhito Tomizawa, MD, PhD; Hideki Matsui, MD, PhD Isao Date, MD, PhD

From Departments of Neurological Surgery (T.O., S.O., T.I., S.A., K.O., K.T., K.S., I.D.) and Physiology (K.T., H.M.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Shikata-cho, Okayama, Japan.

Correspondence to Tomoyuki Ogawa, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558, Japan. E-mail tom{at}md.okayama-u.ac.jp

Background and Purpose— A motif of 11 consecutive arginines (11R) is reported to be one of the most effective protein transduction domains for introducing proteins into the cell membrane. We therefore examined the transduction efficiency of 11R in cerebral arteries.

Methods— Basilar arteries (BAs) obtained from rats were incubated with either 11R-enhanced green fluorescent protein (11R-EGFP) or EGFP without 11R. After incubation, expression of 11R-EGFP or EGFP in BA serial sections was observed by fluorescence microscope. In an additional in vivo experiment, 11R-EGFP or EGFP was injected into the cisterna magna with or without subarachnoid hemorrhage. The 11R-EGFP or EGFP was injected just after the autologous blood injection, and then the expression of 11R-EGFP or EGFP in BA sections was also observed by fluorescence microscope.

Results— The 11R-EGFP signal was much stronger than that of EGFP in all layers of the rat BA, in both in vivo and ex vivo experiments. Moreover, the 11R-EGFP was transduced into the BA immediately (2 hours after the injection). Interestingly, 11R-fused fluorescent protein was transduced especially into the tunica media of the BA.

Conclusions— The 11R-fused fluorescent protein effectively penetrates into all layers of the rat BA, especially into the tunica media. This is the first study to our knowledge to demonstrate the successful transduction of a protein transduction domain fused protein into the cerebral arteries.

Key Words: cerebral vasospasm • cerebrovascular disease protein • enhanced green fluorescence protein • transduction domain