Quantification of poly(ADP-ribose)-modified proteins in cerebrospinal fluid from infants and children after traumatic brain injury

Ericka L. Fink, Yichen Lai, Xiaopeng Zhang, Keri Janesko-Feldman, P. David Adelson, Csaba Szabó, Rachel P. Berger, Ajit A. Sarnaik, Patrick M. Kochanek, Robert S.B. Clark

    Research output: Contribution to journalArticle

    20 Scopus citations

    Abstract

    Poly-ADP-ribosylation (PAR) of proteins by poly(ADP-ribose) polymerases (PARP) occurs after experimental traumatic brain injury (TBI) and modulates neurologic outcome. Several promising pharmacological PARP inhibitors have been developed for use in humans, but there is currently no clinically relevant means of monitoring treatment effects. We therefore used an enzyme-linked immunosorbent assay to measure PAR-modified proteins in cerebrospinal fluid (CSF). Cerebrospinal fluid samples from 17 pediatric TBI patients and 15 controls were plated overnight and then incubated with polyclonal antibody against PAR. Histone-1, a PARP substrate, was incubated with active PARP, NAD, and nicked DNA, and served as the standard. Both peak and mean CSF PAR-modified proteins were increased in TBI patients versus controls. Peak CSF PAR-modified protein levels occurred on day 1 and levels remained increased on day 2 after TBI. Increases in peak CSF PAR-modified protein concentrations were independently associated with age and male sex, but not initial Glasgow Coma Scale score, Glasgow outcome score, or mechanism of injury. The increase in PAR-modified proteins in CSF after TBI may be because of increased PARP activation, decreased PAR degradation, or both. As PAR-modified protein concentration correlated with age and male sex, developmental and sex-dependent roles for PARP after TBI are implicated.

    Original languageEnglish (US)
    Pages (from-to)1523-1529
    Number of pages7
    JournalJournal of Cerebral Blood Flow and Metabolism
    Volume28
    Issue number9
    DOIs
    StatePublished - Sep 1 2008

    Keywords

    • ADP-ribosyltransferase
    • Biomarker
    • Enzyme-linked immunosorbent assay
    • Head injury
    • Poly(ADP-ribose) synthetase
    • Poly(ADPribose) polymerase

    ASJC Scopus subject areas

    • Neurology
    • Clinical Neurology
    • Cardiology and Cardiovascular Medicine

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  • Cite this

    Fink, E. L., Lai, Y., Zhang, X., Janesko-Feldman, K., Adelson, P. D., Szabó, C., Berger, R. P., Sarnaik, A. A., Kochanek, P. M., & Clark, R. S. B. (2008). Quantification of poly(ADP-ribose)-modified proteins in cerebrospinal fluid from infants and children after traumatic brain injury. Journal of Cerebral Blood Flow and Metabolism, 28(9), 1523-1529. https://doi.org/10.1038/jcbfm.2008.52