Suppression of Astroglial Scar Formation and Enhanced Axonal Regeneration Associated with Functional Recovery in a Spinal Cord Injury Rat Model by the Cell Cycle Inhibitor Olomoucine

Objective:To determine if a cell cycle inhibitior, olomoucine, would decrease neuronal cell death, limit astroglial proliferation and production of inhibitory CSPGs, and eventually enhance the functional compensation after SCI in rats. Methods: Three were used as un-operated controls and twelve as sham operated controls. Following spinal cord injury, 48 rats were randomly and blindly assigned to either olomoucine (n=24) or vehicle treatment (n=24) groups. Results: Up-regulations of cell cycle components were closely associated with neuronal cell death and astroglial proliferation as well as the production of CSPGs after SCI. Meanwhile, administration of olomoucine, a selective cell cycle kinase (CDK) inhibitor, has remarkably reduced the up-regulated cell cycle proteins and then decreased neuronal cell death, astroglial proliferation as well as accumulation of CSPGs. More importantly, the treatment with olomoucine has also increased expression of growth-associated proteins-43 (GAP-43), reduced the cavity formation, and improved functional deficits. Conclusion: Suppressing astroglial cell cycle in acute spinal cord injuries is beneficial to axonal growth. in turn, the future therapeutic strategies can be designed to achieve efficient axonal regeneration and functional compensation after traumatic CNS injury.