Effect of Cell Cycle Inhibitor Olomoucine on Astroglial Proliferation and Scar Formation after Focal Cerebral Infarction in Rats

Background:Astrocytes become reactive following many types of CNS injuries.Excessive astrogliosis is detrimental and contributes to neuronal damage.We sought to determine whether inhibition of cell cycle could decrease the proliferation of astroglial cells and therefore reduce excessive gliosis and glial scar formation after focal ischemia.Methods:Cerebral infarction model was induced by photothrombosis method.Rats were examined using MRI,and lesion volumes were estimated on day 3 post-infarction.The expression of glial fibrillary acidic protein(GFAP) and proliferating cell nuclear antigen(PCNA) was observed by immunofluorescence staining.Protein levels for GFAP,PCNA,Cyclin A and Cyclin B1 were determined by Western blot analysis from the ischemic and sham animals sacrificed at 3,7,30 days after operation.Results:Cell cycle inhibitor olomoucine significantly suppressed GFAP and PCNA expression and reduced lesion volume after cerebral ischemia.In parallel studies,we found dense astroglial scar in boundary zone of vehicle-treated rats at 7 and 30 days.Olomoucine can markedly attenuate astroglial scar formation.Western blot analysis showed increased protein levels of GFAP,PCNA,Cyclin A and Cyclin B1 after ischemia,which was reduced by olomoucine treatment.Conclusion: Our results suggested that astroglial activation,proliferation and subsequently astroglial scar formation could be partially inhibited by regulation of cell cycle.Cell cycle modulation thereby provides a potential promising strategy to treat cerebral ischemia.