| 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. | |
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MedLine Citation:
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PMID: 16862564 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It is well established that axons of the adult mammalian CNS are capable of regrowing only a limited amount after injury. Astrocytes are believed to play a crucial role in the failure to regenerate, producing multiple inhibitory proteoglycans, such as chondroitin sulphate proteoglycans (CSPGs). After spinal cord injury (SCI), astrocytes become hypertrophic and proliferative and form a dense network of astroglial processes at the site of lesion constituting a physical and biochemical barrier. Down-regulations of astroglial proliferation and inhibitory CSPG production might facilitate axonal regeneration. Recent reports indicated that aberrant activation of cell cycle machinery contributed to overproliferation and apoptosis of cells in various insults. In the present study, we sought to determine whether 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. Our results showed that 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, and accumulation of CSPGs. More importantly, the treatment with olomoucine has also increased expression of growth-associated proteins-43, reduced cavity formation, and improved functional deficits. We consider that suppressing astroglial cell cycle in acute SCIs is beneficial to axonal growth. In the future, therapeutic strategies can be designed to achieve efficient axonal regeneration and functional compensation after traumatic CNS injury. |
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Authors:
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Dai-Shi Tian; Zhi-Yuan Yu; Min-Jie Xie; Bi-Tao Bu; Otto W Witte; Wei Wang |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of neuroscience research Volume: 84 ISSN: 0360-4012 ISO Abbreviation: J. Neurosci. Res. Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-09-25 Completed Date: 2006-11-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600111 Medline TA: J Neurosci Res Country: United States |
Other Details:
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Languages: eng Pagination: 1053-63 Citation Subset: IM |
Copyright Information:
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Copyright 2006 Wiley-Liss, Inc. |
Affiliation:
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Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Astrocytes / drug effects* Behavior, Animal Blotting, Western / methods Cell Count / methods Cell Cycle Proteins / genetics, metabolism Cell Proliferation / drug effects Cicatrix / drug therapy, pathology Disease Models, Animal Enzyme Inhibitors / therapeutic use* Female Immunohistochemistry / methods In Situ Nick-End Labeling / methods Kinetin / therapeutic use* Nerve Regeneration / drug effects* Nerve Tissue Proteins / metabolism Rats Rats, Sprague-Dawley Recovery of Function / drug effects* Spinal Cord Injuries / drug therapy*, pathology, physiopathology Time Factors Up-Regulation / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/Enzyme Inhibitors; 0/Nerve Tissue Proteins; 0/olomoucine; 525-79-1/Kinetin |
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