Pharmacologic inhibition of poly(ADP-ribose) polymerase is neuroprotective following traumatic brain injury in rats

Journal of Neurotrauma
M C LaPlacaT K McIntosh

Abstract

The nuclear enzyme poly(ADP-ribose) polymerase (PARP), which has been shown to be activated following experimental traumatic brain injury (TBI), binds to DNA strand breaks and utilizes nicotinamide adenine dinucleotide (NAD) as a substrate. Since consumption of NAD may be deleterious to recovery in the setting of CNS injury, we examined the effect of a potent PARP inhibitor, GPI 6150, on histological outcome following TBI in the rat. Rats (n = 16) were anesthetized, received a preinjury dose of GPI 6150 (30 min; 15 mg/kg, i.p.), subjected to lateral fluid percussion (FP) brain injury of moderate severity (2.5-2.8 atm), and then received a second dose 3 h postinjury (15 mg/kg, i.p.). Lesion area was examined using Nissl staining, while DNA fragmentation and apoptosis-associated cell death was assessed with terminal deoxynucleotidyl-transferase-mediated biotin-dUTP nick end labeling (TUNEL) with stringent morphological evaluation. Twenty-four hours after brain injury, a significant cortical lesion and number of TUNEL-positive/nonapoptotic cells and TUNEL-positive/apoptotic cells in the injured cortex of vehicle-treated animals were observed as compared to uninjured rats. The size of the trauma-induced lesion area was significantl...Continue Reading

References

Nov 1, 1992·The Journal of Cell Biology·Y GavrieliS A Ben-Sasson
Jan 1, 1995·Brain Research. Molecular Brain Research·Y LiC Zaloga
Oct 1, 1995·Trends in Biochemical Sciences·T LindahlA Klungland
Jan 1, 1995·Journal of Cell Science. Supplement·T Lindahl
Nov 1, 1996·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·B A StatesF R Sharp
Jan 1, 1997·Stroke; a Journal of Cerebral Circulation·R Schmidt-KastnerA M Hakim
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·J M de MurciaG de Murcia
Aug 1, 1997·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·J P MacManus, M D Linnik
Dec 31, 1997·Journal of Neurotrauma·D H SmithT K McIntosh
Dec 9, 1997·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·K TakahashiJ Zhang
Dec 9, 1997·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·M EndresM A Moskowitz
Aug 15, 1998·Trends in Pharmacological Sciences·C Szabó, V L Dawson
Sep 18, 1998·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·T TokimeK Ueda
Jul 17, 1999·Brain Research. Molecular Brain Research·J A NapieralskiT K McIntosh
Aug 24, 1999·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·M J WhalenP M Kochanek

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Citations

May 19, 2010·Journal of Molecular Modeling·Kazuki OhnoMasaya Orita
Apr 12, 2013·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Bor-Tsang WuFuu-Jen Tsai
Feb 2, 2013·Molecular Aspects of Medicine·Nicola J Curtin, Csaba Szabo
Dec 18, 2003·Neurobiology of Disease·Seong-Woon YuValina L Dawson
Feb 5, 2010·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Bogdan A Stoica, Alan I Faden
Nov 25, 2004·Progress in Biophysics and Molecular Biology·Paul A NguewaJosé M Pérez
Jan 29, 2003·Current Opinion in Pharmacology·N C RoyoT K McIntosh
May 3, 2005·Nature Reviews. Drug Discovery·Prakash Jagtap, Csaba Szabó
Dec 21, 2011·Human Gene Therapy·Min Ki JeeSoo Kyung Kang
Jan 25, 2005·Journal of Neurotrauma·Hilaire J ThompsonTracy K McIntosh
Jul 15, 2009·Journal of Neurotrauma·Masamichi FukushimaRichard L Sutton
Apr 3, 2012·Brain : a Journal of Neurology·Min Ki JeeSoo Kyung Kang
Feb 13, 2001·Nucleic Acids Research·C M Simbulan-RosenthalM E Smulson
Feb 18, 2012·Journal of Neuroinflammation·Joana C d'AvilaRaymond A Swanson
Feb 8, 2005·Critical Care : the Official Journal of the Critical Care Forum·Xiaopeng ZhangRobert S B Clark
Sep 21, 2013·Disease Models & Mechanisms·Mayumi PrinsChristopher C Giza
Oct 29, 2003·The Tohoku Journal of Experimental Medicine·Keiji TabuchiAkira Hara
Jul 12, 2003·Journal of Neurosurgery·Beng Ti AngTseng Tsai Yeo
May 19, 2010·International Journal of Molecular Sciences·Erzsébet KövesdiAndrás Büki
Feb 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Gwen S ScottD Craig Hooper
Jun 20, 2014·The International Journal of Neuroscience·Shun Min XingJunming Tan
Jul 27, 2011·Biochemical Pharmacology·Rosanna Di PaolaSalvatore Cuzzocrea
Nov 3, 2010·Trends in Pharmacological Sciences·David J Loane, Alan I Faden
Feb 6, 2010·Journal of Pharmacological and Toxicological Methods·Laura S LubbersIan J Reynolds
May 29, 2008·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Ericka L FinkRobert S B Clark
Sep 10, 2004·The European Journal of Neuroscience·Seong-Ho KohSeung Hyun Kim
Jun 15, 2004·Brain Pathology·Ramesh Raghupathi
Apr 18, 2009·British Journal of Pharmacology·Valerie C Besson
Aug 26, 2006·The European Journal of Neuroscience·Kang Soo KyungKim Jae Ho
Apr 2, 2014·British Journal of Pharmacology·Amos A FatokunTed M Dawson

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