A possible role of RhoA/Rho-kinase in experimental spinal cord injury in rat.
Secondary injury following traumatic spinal cord injury is induced by the activation of a number of cellular and molecular changes. RhoA, a small GTPase, regulates the organization of the actin cytoskeleton, gene expression, cell proliferation, and has been implicated in the regenerative process. This study was undertaken to investigate the involvement of the RhoA signaling pathway in the secondary injury that follows traumatic spinal cord injury in rats. RhoA mRNA and protein expressions were enhanced significantly in the injured spinal cord 1 week after surgery (P<0.05, ANOVA). C3 exozyme (RhoA inhibitor), Y-27632 (selective Rho kinase inhibitor), and Fasudil (non-selective protein kinase inhibitor) were administered after spinal cord injury, and the subjects were evaluated for 5 weeks as per BBB locomotor score. Poor rat response interrupted the C3 experiment. Y-27632 slightly, but significantly (P<0.05, ANOVA), delayed the recovery. Fasudil significantly improved the BBB score (P<0.05, ANOVA). In conclusion, spinal cord injury activates the RhoA/Rho-kinase alpha, beta associated pathway. However, their role in secondary injury or in the improvement of functional recovery remains unclear. Fasudil might exert a cytoprotective effect by mechanisms other than inhibiting Rho-kinase alpha, beta.
Sung
Joo Kyung
JK
Department of Neurosurgery, University of Mississippi Medical Center, Jackson, MS, USA.
Miao
Liyan
L
Calvert
John W
JW
Huang
Lixin
L
Louis Harkey
H
H
Zhang
John H
JH
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D036002:ADP Ribose Transferases / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001905:Botulinum Toxins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D009043:Motor Activity / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011506:Proteins / Q000032:analysis; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D011725:Pyridines; D012333:RNA, Messenger; C108830:Y 27632; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D001905:Botulinum Toxins; D020742:rhoA GTP-Binding Protein; C049347:fasudil