Differential effects of two ROCK inhibitors, Fasudil and Y-27632, on optic nerve regeneration in adult cats

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• 作者：Masahiro Ichikawa ; Jun Yoshida ; Kiyoshi Saito ; Hiroe Sagawa ; Yoshihito Tokita ; Masami Watanabe
• 关键词：Axonal regeneration ; ROCK inhibitor ; Retinal culture ; Neurite extension ; Optic nerve crush ; Adult cat
• 刊名：Brain Research
• 出版年：2008
• 出版时间：27 March 2008
• 年：2008
• 卷：1201
• 期：Complete
• 页码：23-33
• 全文大小：1360 K

文摘

A ROCK inhibitor Fasudil is widely administered to relieve vasospasm in patients after subarachnoid hemorrhage in Japan. We investigated the difference of Fasudil and Y-27632, a common ROCK inhibitor, on neurite regeneration in culture and axonal regeneration after injuring the optic nerve (OpN) in cats. The optimal dose of Y-27632, determined by counting the number and length of neurites in retinal explants, was found to be 100µM: the only effect of Fasudil was to promote extension of glial processes. We next examined the effects of Fasudil (10 µM–100 µM) and Y-27632 (10 µM–300 µM) on axonal regeneration in the crushed OpN model in vivo. Immediately after crushing the left OpN, Fasudil or Y-27632 was injected into the vitreous and the crushed site. Injection of 10 µM and 100 µM Y-27632 induced extension of the optic axons beyond the crush site, with the latter dosage giving stronger regeneration. Very few axons passed beyond the crush site in the optic nerve with phosphate-buffered saline injection, and no axons elongated in the OpN with Fasudil injection.