Korean J Anesthesiol.  2002 Feb;42(2):228-240. 10.4097/kjae.2002.42.2.228.

Effects of Poly (ADP-ribose) Polymerase Inhibitor on Hypoxic-ischemic Injury in the Neonatal Rat Brain: 1H Magnetic Resonance Spectroscopic Study

Affiliations
  • 1Department of Anesthesiology, Ulsan University College of Medicine, Seoul, Korea. phpark@www.amc.seoul.kr
  • 2Department of NMR Laboratory, Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea.
  • 3Boston Children's Hospital, Boston, USA.

Abstract

BACKGROUND: Poly (ADP-ribose) polymerase (PARP) has been described as an important candidate for mediation of neurotoxicity after brain ischemia. This study was purposed to evaluate the effects of a PARP inhibitor on hypoxic-ischemic injury in the neonatal rat brain. In this study, a highly potent inhibitor of PARP, 3, 4-Dihydro-5-[4-(1-piperidinyl) butoxy]-1 (2H)-isoquinolinone (DPQ) was investigated.
METHODS
Seven-day old Sprague-Dawley rat pups were used. The right common carotid artery was ligated under halothane anesthesia. After a recovery period of 3 hours, they were exposed to 8% oxygen at 37degreesC for about 120 minutes. The animals were divided into four groups: the pre-treatment group (n = 13) and post-treatment group (n = 21) were given DPQ 10 mg/kg and the pre-control group (n = 7) and post-control group (n = 14) were given a vehicle for controls. Pre-treatment and pre-control groups were injected 30 minutes prior to the hypoxic injury while post-treatment and post-control groups were injected 30 minutes after the hypoxic period intraperitoneally. The right cerebral hemisphere of the rats were examined with localized (1)H magnetic resonance spectroscopy on day 1 and 7 after the hypoxic insult. Lipid/N-acetyl aspartate (Lip/NAA) and lipid/creatine (Lip/Cr) ratios were used as apoptotic markers. On day 14, the degree of brain injury was scored by morphological changes.
RESULTS
In the DPQ treated groups, the Lip/NAA and Lip/Cr ratios were lower than those of the control groups on day 1 after the hypoxic-ischemic injury (P < 0.05). However on day 7, only the ratios of the pre-treatment group were lower than those of the control group (P < 0.05). The degree of morphological changes of the brain injury on day 14 were lower in the DPQ treated groups (P < 0.05).
CONCLUSIONS
These results suggest that DPQ exerts a neuroprotective effect in cerebral hypoxic-ischemic injury probably by inhibiting apoptosis especially in the early stage after an insult. Acute inhibition of PARP can have a therapeutic value in preventing ischemic brain injury.

Keyword

3, 4-Dihydro-5-[4-(1-piperidinyl) butoxy]-1 (2H)-isoquinolinone; (1)H magnetic resonance spectroscopy; hypoxic-ischemic brain injury
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