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Cell-specific DNA fragmentation may be attenuated by a survivin-dependent mechanism after traumatic brain injury in rats

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Abstract

Survivin attenuates apoptosis by inhibiting cleavage of some cell proteins by activated caspase-3. We recently discovered strong up-regulation of survivin, primarily in astrocytes and a sub-set of neurons, after traumatic brain injury (TBI) in rats. In this study we characterized co-expression of survivin with activated caspase-3 and downstream DNA fragmentation (TUNEL) in astrocytes and neurons after TBI. Western blot analysis revealed significant time-dependent increases in active caspase-3 between 5 and 14 days post-injury. No difference was observed between the proportion of survivin-positive and survivin-negative cells labeled with active caspase-3 at 5 or 7 days post-injury, as indicated by dual fluorescent immunostaining. Labeling of survivin-negative cells with TUNEL was, however, significantly greater than for survivin-positive cells, suggesting that expression of survivin may attenuate DNA cleavage and progression of apoptosis. A higher proportion of astrocytes than neurons accumulated active caspase-3. In contrast, co-localization with TUNEL was significantly higher for neurons than for astrocytes. These data suggest that survivin expression may attenuate DNA cleavage and cell death, and that this mechanism operates in a cell type-specific manner after TBI.

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Abbreviations

IAP:

Inhibitor of apoptosis protein

IHC:

Immunohistochemistry

TBI:

Traumatic brain injury

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Acknowledgments

We thank Barbara O’Steen and Jeremy Flint for technical assistance. We also thank Edward Lin and Karie Johnson, MESS ATC for assistance with cell quantification. This work was funded by grants NIH RO1 NS39091, NIH RO1 NS40182, DAMD 17-99-1-9565, DAMD 17-01-1-0765, and DAMD 17-03-1-0066.

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Authors and Affiliations

  1. Center for Traumatic Brain Injury Studies (CTBIS), E.F and W.L. McKnight Brain Institute of the University of Florida, Gainesville, FL, 32610, USA

    Erik A. Johnson, Stanislav I. Svetlov, Kevin K. W. Wang, Ronald L. Hayes & Jose A. Pineda

  2. Department of Neuroscience, E.F and W.L. McKnight Brain Institute of the University of Florida, 100 S Newell Dr. Bldg. 59, L1 100, Gainesville, FL, 32610, USA

    Erik A. Johnson, Stanislav I. Svetlov, Kevin K. W. Wang & Ronald L. Hayes

  3. Department of Pediatrics, E.F and W.L. McKnight Brain Institute of the University of Florida, 100 S Newell Dr. Bldg. 59, L1-118, Gainesville, FL, 32610, USA

    Jose A. Pineda

  4. Department of Pediatrics, Washington University School of Medicine, Campus Box 8116, St. Louis, MO, 63110, USA

    Jose A. Pineda

  5. Department of Anatomy and Cell Biology, E.F and W.L. McKnight Brain Institute of the University of Florida, Gainesville, FL, 32610, USA

    Ronald L. Hayes

  6. Department of Psychiatry, E.F and W.L. McKnight Brain Institute of the University of Florida, c100 S Newell Dr. Bldg. 59, L4-100, Gainesville, FL, 32610, USA

    Kevin K. W. Wang & Ronald L. Hayes

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  1. Erik A. Johnson
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  2. Stanislav I. Svetlov
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  5. Jose A. Pineda
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Correspondence to Jose A. Pineda.

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Johnson, E.A., Svetlov, S.I., Wang, K.K.W. et al. Cell-specific DNA fragmentation may be attenuated by a survivin-dependent mechanism after traumatic brain injury in rats. Exp Brain Res 167, 17–26 (2005). https://doi.org/10.1007/s00221-005-2362-2

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  • DOI: https://doi.org/10.1007/s00221-005-2362-2

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