Delayed treatment with Rho-kinase inhibitor does not enhance axonal regeneration or functional recovery after spinal cord injury in rats

• Published in: Experimental neurology 2006-08, Vol.200 (2), p.392-397
• Main Authors: Nishio, Yutaka, Koda, Masao, Kitajo, Keiko, Seto, Minoru, Hata, Katsuhiko, Taniguchi, Junko, Moriya, Hideshige, Fujitani, Masashi, Kubo, Takekazu, Yamashita, Toshihide
• Format: Article
• Language: English
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - administration & dosage; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; Animals; Axon; Behavior, Animal - drug effects; Biological and medical sciences; Biotin - analogs & derivatives; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dextrans; Disease Models, Animal; Drug Administration Schedule; Enzyme Inhibitors - administration & dosage; Immunohistochemistry - methods; Injuries of the nervous system and the skull. Diseases due to physical agents; Intracellular Signaling Peptides and Proteins; Male; Medical sciences; Motor Activity - drug effects; Nerve Regeneration - drug effects; Neurology; Neuron; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Pyramidal Tracts - drug effects; Pyramidal Tracts - pathology; Rats; Rats, Wistar; Recovery of Function - drug effects; Regeneration; rho-Associated Kinases; Rho-kinase; Spinal cord; Spinal Cord Injuries - drug therapy; Statistics, Nonparametric; Time Factors; Traumas. Diseases due to physical agents
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2006.02.123

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.