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

作　　者：ZHANG Gui-bin TIAN Dai-shi XU Yun-lan XIE Min-jie WANG Ping DU Yi-xing WANG Wei 

机构地区：[1]Department of Neurology, Xiangyang No. 1 People＇s Hospital of Hubei Medical College, Hu-bei 441000, China [2]Department of Neurology, Tongji Hospital, Tongji Medical College, HuazhongUniversity of Science and Technology, Wuhan 430030, China

出　　处：《神经损伤与功能重建》2011年第5期328-335,共8页Neural Injury and Functional Reconstruction

基　　金：This study was supported by a grant from the National Nature Science Foundation of China(No.30230140,30400142)

摘　　要：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.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

关 键 词：PROLIFERATION astrocytic scar cell cycle CYCLINS cyclin dependent kinase OLOMOUCINE cerebral infarction 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学]