DOI: 10.1073/pnas.0500989102. Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury

Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury

10.1073/pnas.0500989102

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

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.

Bibliography

Di Giovanni, S., Movsesyan, V., Ahmed, F., Cernak, I., Schinelli, S., Stoica, B., & Faden, A. I. (2005). Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury. Proceedings of the National Academy of Sciences, 102(23), 8333â8338.

Authors 7

Simone Di Giovanni (first)
Vilen Movsesyan (additional)
Farid Ahmed (additional)
Ibolja Cernak (additional)
Sergio Schinelli (additional)
Bogdan Stoica (additional)
Alan I. Faden (additional)

References 42 Referenced 328

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Dates

Type	When
Created	20 years, 3 months ago (May 27, 2005, 10:06 p.m.)
Deposited	3 years, 4 months ago (April 25, 2022, 10:41 p.m.)
Indexed	48 minutes ago (Sept. 3, 2025, 2:52 a.m.)
Issued	20 years, 3 months ago (May 27, 2005)
Published	20 years, 3 months ago (May 27, 2005)
Published Online	20 years, 3 months ago (May 27, 2005)
Published Print	20 years, 2 months ago (June 7, 2005)

Funders 0

None

BibTeX

@article{Di_Giovanni_2005, title={Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0500989102}, DOI={10.1073/pnas.0500989102}, number={23}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Di Giovanni, Simone and Movsesyan, Vilen and Ahmed, Farid and Cernak, Ibolja and Schinelli, Sergio and Stoica, Bogdan and Faden, Alan I.}, year={2005}, month=may, pages={8333–8338} }

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