@article{237b423264c24e7cb89662e007a8d178,
title = "A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord",
abstract = "Axons in the adult mammalian central nervous system (CNS) exhibit little regeneration after injury. It has been suggested that several axonal growth inhibitors prevent CNS axonal regeneration. Recent research has demonstrated that semaphorin3A (Sema3A) is one of the major inhibitors of axonal regeneration. We identified a strong and selective inhibitor of Sema3A, SM-216289, from the fermentation broth of a fungal strain. To examine the effect of SM-216289 in vivo, we transected the spinal cord of adult rats and administered SM-216289 into the lesion site for 4 weeks. Rats treated with SM-216289 showed substantially enhanced regeneration and/or preservation of injured axons, robust Schwann cell-mediated myelination and axonal regeneration in the lesion site, appreciable decreases in apoptotic cell number and marked enhancement of angiogenesis, resulting in considerably better functional recovery. Thus, Sema3A is essential for the inhibition of axonal regeneration and other regenerative responses after spinal cord injury (SCI). These results support the possibility of using Sema3A inhibitors in the treatment of human SCI.",
author = "Shinjiro Kaneko and Akio Iwanami and Masaya Nakamura and Akiyoshi Kishino and Kaoru Kikuchi and Shinsuke Shibata and Okano, {Hirotaka J.} and Takeshi Ikegami and Ayako Moriya and Osamu Konishi and Chikao Nakayama and Kazuo Kumagai and Toru Kimura and Yasufumi Sato and Yoshio Goshima and Masahiko Taniguchi and Mamoru Ito and Zhigang He and Yoshiaki Toyama and Hideyuki Okano",
note = "Funding Information: We are grateful to L. Benowitz (Children{\textquoteright}s Hospital Boston); H. Fujisawa (Nagoya University); A.L. Kolodkin (Johns Hopkins University); and Y. Ihara and K. Mori (Tokyo University) for reagents. We also thank M. Dezawa, S. Kawabata, U. Uchida, Y. Sugiyama, F. Nakamura, T. Nagai, S. Miyao, T. Harada, K. Watanabe, H. Hanafusa, Y. Ujimasa, T. Yagi and G. Yiu for technical assistance. We are also grateful to T. Takahashi, H. Fujisawa and F. Murakami for their critical reading of the manuscript, to the members of the Okano Laboratory for their comments on the manuscript. This work was supported by grants from the Leading Project for Realization of Regenerative Medicine from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan; the Japan Science and Technology Corporation (JST); and the General Insurance Association of Japan. This work was also supported by a Keio University special grant-in-aid for innovative collaborative research projects to H.O.; a Keio University grant-in-aid for encouragement of young medical scientists to S.K. and A.I.; and a grant-in-aid from the 21st Century COE Program of MEXT, Japan, to Keio University.",
year = "2006",
month = dec,
doi = "10.1038/nm1505",
language = "English",
volume = "12",
pages = "1380--1389",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "12",
}