Biphasic changes in the levels of poly(ADP-ribose) polymerase-1 and caspase 3 in the immature brain following hypoxia-ischemia

Shannon S. Martin, J. Regino Perez-Polo, Kristin M. Noppens, Marjorie R. Grafe

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    Abstract

    Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA repair-associated enzyme that has multiple roles in cell death. This study examined the involvement of PARP-1 in ischemic brain injury in the 7-day old rat, 0.5-48 h after unilateral carotid artery ligation and 2 h of 7.8% oxygen. This experimental paradigm produced a mild to moderate injury; 40-67% of animals in the ligated groups had histological evidence of neuronal death. Ipsilateral cortical injury was seen at all survival times, while mild contralateral cortical injury was seen only at the 1 h survival time. Hippocampal injury was delayed relative to the cortex and did not show a biphasic pattern. Immunohistochemical staining for PARP showed bilateral increased staining as early as 1 h post-hypoxia. PARP staining at early time periods was most intense in layer V of cortex, but did not demonstrate a pattern of cell clusters or columns. Ipsilateral PARP-1 levels quantified by western blotting showed a biphasic pattern of elevation with peaks at 0.5 and 12 h post-hypoxia. Contralateral PARP-1 levels were also elevated at 0.5 and 24 h. PARP activity as determined by immunoreactivity for poly(ADP-ribose) (PAR) was increased ipsilaterally at 0.5, 2 and 12 h survival times. Cortical caspase 3-activity was increased ipsilaterally at 6, 12, and 24 h and contralaterally at 0.5, 1, 2 and 6 h post-hypoxia. There are three main findings in this study. First, changes in the distribution and amount of cell death correlate well with measured PARP-1 levels after hypoxia-ischemia, and both display biphasic characteristics. Second, there are significant early, transient morphological and biochemical changes in the contralateral cortex after neonatal hypoxia-ischemia due to unilateral permanent occlusion of a carotid artery followed by 2 h of systemic hypoxia. Third, variability in the responses of individual pups to hypoxia-ischemia suggests the presence of unidentified confounding factors.

    Original languageEnglish (US)
    Pages (from-to)673-686
    Number of pages14
    JournalInternational Journal of Developmental Neuroscience
    Volume23
    Issue number8
    DOIs
    StatePublished - Dec 2005

    Fingerprint

    Brain Hypoxia-Ischemia
    Caspase 3
    Ischemia
    Wounds and Injuries
    Staining and Labeling
    Carotid Arteries
    Cell Death
    DNA Repair Enzymes
    Poly Adenosine Diphosphate Ribose
    Poly (ADP-Ribose) Polymerase-1
    Hypoxia
    Brain Injuries
    Ligation
    Western Blotting
    Oxygen

    Keywords

    • Brain
    • Cell death
    • Hypoxia
    • Ischemia
    • Neonatal
    • PARP-1
    • Rat

    ASJC Scopus subject areas

    • Developmental Biology
    • Developmental Neuroscience

    Cite this

    Biphasic changes in the levels of poly(ADP-ribose) polymerase-1 and caspase 3 in the immature brain following hypoxia-ischemia. / Martin, Shannon S.; Perez-Polo, J. Regino; Noppens, Kristin M.; Grafe, Marjorie R.

    In: International Journal of Developmental Neuroscience, Vol. 23, No. 8, 12.2005, p. 673-686.

    Research output: Contribution to journalArticle

    Martin, Shannon S. ; Perez-Polo, J. Regino ; Noppens, Kristin M. ; Grafe, Marjorie R. / Biphasic changes in the levels of poly(ADP-ribose) polymerase-1 and caspase 3 in the immature brain following hypoxia-ischemia. In: International Journal of Developmental Neuroscience. 2005 ; Vol. 23, No. 8. pp. 673-686.
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    AU - Grafe, Marjorie R.

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