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Poly(ADP-ribose) polymerase during reperfusion after transient forebrain ischemia

Its role in brain edema and cell death

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Abstract

The activation of poly(ADP-ribose) polymerase (PARP) in the reperfused brain after ischemia has been assumed but never has been directly presented. Our studies indicate a different dynamic of PARP activity alteration in hippocampus during reperfusion after 3 and 10 min of transient forebrain ischemia in gerbils. The phasic stimulation of PARP activity was observed during reperfusion 15 min, 120 min, and 4 d after 3 min of ischemia with subsequent lowering of its activity close to control value on the seventh day of reperfusion. After 10 min of ischemic insult, PARP activity significantly increased from the third to the seventh day of reperfusion. The protein level of PARP was not significantly changed during reperfusion after 3 and 10 min of ischemia, with one exception: On the third day after 10 min of ischemia, PARP protein level was 28% lower compared to control; however, no enhancement of 85-kDa protein immunoreactivity was observed. These data indicate the lack of PARP cleavage in hippocampus of gerbils subjected to ischemia-reperfusion injury. The inhibitor of PARP, 3-aminobenzamide (3-AB) in a dose of 30 mg/kg b.w. (body weight) injected intravenously directly after 3 min of ischemia protects >60% of neuronal cells against death in the CA1 layer of hippocampus but has no effect after 10 min of ischemic episode. 3-AB decreased forebrain edema significantly after 3 and 10 min of ischemia. Our data indicate that PARP inhibitor(s) might offer a potent therapeutic strategy for short global ischemia. The combination of PARP inhibitor with potent antioxidant might enhance its ameliorating effect.

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Authors and Affiliations

  1. Department of Neurophysiology, Polish Academy of Sciences, Warsaw, Poland

    Robert P. Strosznajder

  2. Department of Neuropathology, Polish Academy of Sciences, Warsaw, Poland

    Roman Gadamski

  3. Department of Cellular Signaling, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

    Grzegorz A. Czapski, Henryk Jesko & Joanna B. Strosznajder

Authors
  1. Robert P. Strosznajder
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  2. Roman Gadamski
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  3. Grzegorz A. Czapski
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  4. Henryk Jesko
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  5. Joanna B. Strosznajder
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Correspondence to Robert P. Strosznajder.

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Strosznajder, R.P., Gadamski, R., Czapski, G.A. et al. Poly(ADP-ribose) polymerase during reperfusion after transient forebrain ischemia. J Mol Neurosci 20, 61–71 (2003). https://doi.org/10.1385/JMN:20:1:61

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  • DOI: https://doi.org/10.1385/JMN:20:1:61

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