title: Delayed treatment with Rho-kinase inhibitor does not enhance axonal regeneration or functional recovery after spinal cord injury in rats.
abstract: Axonal regeneration in the central nervous system is blocked by many different growth inhibitory factors. Some of these inhibitors act on neurons by activating RhoA and Rho-kinase, an effector of RhoA. Several studies have shown that Rho-kinase inhibition immediately after spinal cord injury enhances axonal sprouting and functional recovery. In this study, we ask whether delayed treatment with Rho-kinase inhibitor is effective in promoting regeneration and functional recovery. We administered Fasudil, a Rho-kinase inhibitor, locally to the injury site 4 weeks or immediately after contusion of the thoracic spinal cord in rats. Although the immediate treatment significantly stimulated axonal sprouting and recovery of hindlimb function, treatment started 4 weeks after surgery had no effect on fiber sprouting or locomotor recovery. Our findings suggest that RhoA/Rho-kinase alone may not account for the irreversible arrest of axon outgrowth in the chronic stage of injury in the central nervous system.
authors.affiliation: Department of Neurobiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nishio
authors.forename: Masao
authors.initials: M
authors.lastname: Koda
authors.forename: Keiko
authors.initials: K
authors.lastname: Kitajo
authors.forename: Minoru
authors.initials: M
authors.lastname: Seto
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hata
authors.forename: Junko
authors.initials: J
authors.lastname: Taniguchi
authors.forename: Hideshige
authors.initials: H
authors.lastname: Moriya
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujitani
authors.forename: Takekazu
authors.initials: T
authors.lastname: Kubo
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001710:Biotin / Q000031:analogs & derivatives; D003911:Dextrans; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D018709:Statistics, Nonparametric; D013997:Time Factors; D054460:rho-Associated Kinases
chemical_list: D003911:Dextrans; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; C076397:biotinylated dextran amine; D001710:Biotin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C049347:fasudil