Post-treatment with a novel PARG inhibitor reduces infarct in cerebral ischemia in the rat

Xi Chun M Lu, Edmond Massuda, Qian Lin, Weixing Li, Jia He Li, Jie Zhang

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Poly(ADP-ribose) is synthesized from nicotinamide adenine dinucleotide (NAD+) by poly(ADP-ribose) polymerase (PARP) and degraded by poly(ADP-ribose) glycohydrolase (PARG). Overactivation of the poly(ADP-ribose) pathway increases nicotinamide and decreases cellular NAD+/ATP, which leads to cell death. Blocking poly(ADP-ribose) metabolism by inactivating PARP has been shown to reduce ischemia injury. We investigated whether disrupting the poly(ADP-ribose) cycle by PARG inhibition could achieve similar protection. We demonstrate that either pre- or post-ischemia treatment with 40 mg/kg of N-bis-(3-phenyl-propyl)9-oxo-fluorene-2,7-diamide, a novel PARG inhibitor, significantly reduces brain infarct volumes by 40-53% in a rat model of focal cerebral ischemia. Our result provides the first evidence that PARG inhibitors can ameliorate ischemic brain damage in vivo, in support of PARG as a new therapeutic target for treating ischemia injury.

Original languageEnglish (US)
Pages (from-to)99-103
Number of pages5
JournalBrain Research
Issue number1-2
StatePublished - Jul 18 2003
Externally publishedYes


  • Cell death
  • Ischemia and reperfusion
  • Middle cerebral artery occlusion
  • Neuroprotection
  • PARG
  • PARP
  • Stroke
  • Therapeutic target

ASJC Scopus subject areas

  • Neuroscience(all)


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