Differential effects of two ROCK inhibitors, Fasudil and Y-27632, on optic nerve regeneration in adult cats.
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 100 microM: the only effect of Fasudil was to promote extension of glial processes. We next examined the effects of Fasudil (10 microM-100 microM) and Y-27632 (10 microM-300 microM) 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 microM and 100 microM 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.
Ichikawa
Masahiro
M
Department of Neurosurgery, Nagoya University Graduate School of Medicine, Tsuruma-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Yoshida
Jun
J
Saito
Kiyoshi
K
Sagawa
Hiroe
H
Tokita
Yoshihito
Y
Watanabe
Masami
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000577:Amides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002415:Cats; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D008297:Male; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009900:Optic Nerve / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D009924:Organ Culture Techniques; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D012160:Retina / Q000166:cytology / Q000187:drug effects; D016896:Treatment Outcome; D014855:Wallerian Degeneration / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000577:Amides; D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil