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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Stoica, Bogdan Schinelli, Sergio Movsesyan, Vilen Ahmed, Farid Cernak, Ibolja Di Giovanni, Simone Faden, Alan I. |
| Description | Author Affiliation: Di Giovanni S ( Department of Neuroscience, Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington, DC 20057, USA.); |
| Abstract | Traumatic brain injury (TBI) causes neuronal apoptosis, inflammation, and reactive astrogliosis, which contribute to secondary tissue loss, impaired regeneration, and associated functional disabilities. Here, we show that up-regulation of cell cycle components is associated with caspase-mediated neuronal apoptosis and glial proliferation after TBI in rats. In primary neuronal and astrocyte cultures, cell cycle inhibition (including the cyclin-dependent kinase inhibitors flavopiridol, roscovitine, and olomoucine) reduced up-regulation of cell cycle proteins, limited neuronal cell death after etoposide-induced DNA damage, and attenuated astrocyte proliferation. After TBI in rats, flavopiridol reduced cyclin D1 expression in neurons and glia in ipsilateral cortex and hippocampus. Treatment also decreased neuronal cell death and lesion volume, reduced astroglial scar formation and microglial activation, and improved motor and cognitive recovery. The ability of cell cycle inhibition to decrease both neuronal cell death and reactive gliosis after experimental TBI suggests that this treatment approach may be useful clinically. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 23 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Brain Injuries Pathology Cell Cycle Drug Effects Cicatrix Prevention & Control Neuroglia Cytology Neuroprotective Agents Pharmacology Animals Apoptosis Astrocytes Drug Therapy Caspase 3 Caspases Metabolism Cell Proliferation Cell Survival Cells, Cultured Cyclin D1 Cyclin-Dependent Kinases Antagonists & Inhibitors DNA Damage Etoposide Flavonoids Gene Expression Regulation Therapeutic Use Piperidines Protein Kinase Inhibitors Rats, Sprague-Dawley Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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