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A possible role of RhoA/Rho-kinase in experimental spinal cord injury in rat
Joo Kyung Sung1, Liyan Miao, John W Calvert
1Department of Neurosurgery, University of Mississippi Medical Center, Jackson, MS, USA.
Abstract:
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.
Insights
Spinal cord injury activates the RhoA pathway. While its role in recovery is unclear, Fasudil treatment improved locomotor function in rats, suggesting potential cytoprotective effects beyond Rho-kinase inhibition.
Area of Science:
- Neuroscience
- Molecular Biology
- Regenerative Medicine
Background:
- Traumatic spinal cord injury (SCI) triggers secondary injury cascades involving cellular and molecular changes.
- RhoA, a small GTPase, influences actin cytoskeleton, gene expression, and cell proliferation, impacting regeneration.
- The RhoA signaling pathway's specific role in SCI secondary injury requires further investigation.
Purpose of the Study:
- To investigate the involvement of the RhoA signaling pathway in secondary injury following traumatic spinal cord injury in rats.
- To evaluate the effects of RhoA pathway inhibitors on functional recovery after SCI.
Main Methods:
- Rats underwent spinal cord injury, and RhoA mRNA and protein expression were assessed.
- Administration of C3 exozyme (RhoA inhibitor), Y-27632 (ROCK inhibitor), and Fasudil (protein kinase inhibitor) post-SCI.
- Locomotor recovery was evaluated using the BBB (Basso, Beattie, Bresnahan) scale over 5 weeks.
Main Results:
- RhoA mRNA and protein expression significantly increased in the injured spinal cord 1 week post-surgery.
- Y-27632 administration slightly but significantly delayed locomotor recovery.
- Fasudil administration significantly improved the BBB locomotor score.
Conclusions:
- Spinal cord injury activates the RhoA/Rho-kinase pathway.
- The precise role of this pathway in secondary injury and functional recovery remains uncertain.
- Fasudil may offer cytoprotective benefits through mechanisms independent of Rho-kinase inhibition.