Table 3

Protection against various forms of neuronal injury by pharmacological inhibition or genetic inactivation of PARP in vitro and in vivo

Experimental ModelInducer of InjuryMode of PARP InhibitionEffect of PARP InhibitionReference
Rat hippocampal neuronsNitric oxide3-AB, nicamImproved neuronal conductance Wallis et al., 1993
Rat cortical culturesNMDA, SNAPBenzamide, 3-AB, ISQReduced cell death Zhang et al., 1994
Cerebellar granule cellsGlutamateBenzamide, 3-AB, 3-APHReduced cell death Cosi et al., 1994
Rat cortical culturesNMDA, SNAP, SIN-1PARP−/−phenotype, benzamide, DHQReduced cell death Eliasson et al., 1997
NSC39 spinal cord linePeroxynitrite, H2O2 Benzamide, nicam, 3-AB, PHTReduced cell death Cookson et al., 1998
Cerebellar granule neurons3-Acetylpyridine3-ABProtection against cell death Wullner et al., 1997
Rat cortexH2O2 Benzamide, nicamReduced cell death Hivert et al., 1998
C6 astrocytoma cellsPeroxynitriteINH2BPReduced cell death Endres et al., 1998b
Rat motoneuronsOGD3-methoxybenzamideReduction of ATP depletion Tasker et al., 1998
Rat hippocampal neuronsHomocysteine3-ABReduction of NAD depletion and cell necrosis Kruman et al., 2000
Rat hippocampal neuronsSIN-1, NOC-9NicamReduction of cell necrosis and apoptosis Lin et al., 2000
Mouse neurons and astrocytesH2O2, NMDA, MNNGBenzamide, PARG inhibitors gallotannin and nobotanin BReduction of cell necrosis Ying and Swanson, 2000; Ying et al., 2001
Mixed rat cortical cellsOGDBenzamide, PHT, DPQReduction of cell necrosis Moroni et al., 2001
Mixed rat cortical cellsOGDPJ34Reduction of cell necrosis Abdelkarim et al., 2001
Hippocampal slicesOGDBenzamide, PHT, DPBNo effect on apoptotic death Moroni et al., 2001
Hippocampal slicesFluid percussion injury3-ABImproved neuronal conductance Wallis et al., 1996
Rat cortical slicesH/RBenzamide, 3-AB, ISQReduced LDH leakage Oka et al., 2000
Human A72 gliomaH2O2 3-ABReduced cell death, maintained ATP Lee et al., 2001
Mouse BV-2 microglia mouse hippocampal culturesNMDAPARP−/−phenotypeAmelioration of glial migration and of secondary neuronal injury Ullrich et al., 2001b
MouseMCAo I/RPARP−/− phenotype, 3-ABReduced infarct size, maintained NAD, improved neurological function, both short-term and after several days Eliasson et al., 1997;Endres et al., 1997; Goto et al., 2002
RatMCAo, BCo, I/RDPQReduced infarct size, improved neurological status; at high doses DPQ loses protective effect Takahashi et al., 1997, 1999
RatMCAo I/R3-ABReduced infarct size, attenuation in glutamate and PEA release Lo et al., 1998
RatMCAo3-ABReduced infarct size Tokime et al., 1998
MouseMCAo, I/RINH2BPReduced infarct size, improved neurological status Endres et al., 1998b
RatMCAo I/R3-AB, nicamReduced infarct size, improved neurological status; at high doses nicam becomes detrimental Sun and Cheng, 1998
Neonatal ratMCAo I/R3-ABReduced infarct size, improved neurological status both short- (2 days) and long-term (17 days), reduced neutrophil infiltration, reduced nitrosative stress Ducrocq et al., 2000
Mouse, ratMCAo I/RPJ34Reduced infarct size, improved neurological status Abdelkarim et al., 2001
RatMCAoPJ34Reduced infarct at 4 h permanent MCAo Abdelkarim et al., 2001
RatGlobal brain ischemia3-ABReduced infarct, improved cortical NAD and phosphocreatine levels, no change in ATP Plaschke et al., 2000a
RatMCAo I/R3-ABLong-term (28 days) improvement in neurological status and reduced infarct volume Ding et al., 2001
RatMCAoNicamReduced infarct size, improved neurological status both with short-term (1 day) and delayed (7 days) determinations; the protective effect diminishes at higher doses of the compound Ayoub et al., 1999; Mokudai et al., 2000; Sakakibara et al., 2000; Ayoub and Maynard, 2002
MouseCortical traumaPARP−/− phenotypeImproved neurological function Whalen et al., 1999
RatCortical traumaGPI 6150Reduced lesion size, protection from cell death LaPlaca et al., 2001
MouseIntrastriatal NMDAPARP−/− phenotypeProtection from cell death Mandir et al., 2000
Mouseintrastriatal AMPAPARP−/− phenotypeNo protection from cell death Mandir et al., 2000
Mouset-BuOOH (i.c.v.)NicamMaintenance of NAD, NADP, and NADPH levels in many brain regions Klaidman et al., 1996, 2001
GerbilShort BCoBenzamide, PHT, DPB-ISQNo effect on hippocampal apoptotic death Moroni et al., 2001
RatShort global ischemia and hypothermia3-ABEnhancement of CA1 hippocampal apoptotic death Nagayama et al., 2000
MouseMonocular deprivationPARP−/− phenotypeProtection from cell death in dLGN Nucci et al., 2001
RatCCIBenzamideReduced neuronal death, reduced hyperalgesia and mechano-allodynia Mao et al., 1997
RatSomanBenzamideReduction in neuronal deficit, improved survival Meier et al., 1999
MouseMPTPPARP−/− phenotypeReduced cell death, improved function, protection against dopamine loss Mandir et al., 1999
MouseMPTPBenzamide, ISQMaintained striatal NAD and ATP protection against dopamine loss Cosi et al., 1996; Cosi and Marien, 1999
RatMPP(+)3-ABNo protection against the impairment of neuronal dopamine transporter activity Barc et al., 2001
MouseNigral graftingPARP−/− phenotypeNo improvements in implanted cell survival or graft recipient status Kaminski et al., 1999
Guinea pigI/R of the cochlea3-ABImproved neuronal conductance Tabuchi et al., 2001
RatI/R of the retina3-ABReduced cell death Lam, 1997; Chiang and Lam, 2000
Newborn piglet E. coli meningitis3-ABDecrease in lactate production, neutrophil infiltration, TNF production, peroxidation and ATP depletion Park et al., 2001
Mouse, rat E. coli meningitis3-AB, PARP−/− phenotypeDecrease in inflammatory mediator production, improved survival and CNS function Koedel et al., 2002
RabbitSAH3-ABAttenuated vasospasm Satoh et al., 2001
  • 3-AB, 3-aminobenzamide; nicam, nicotinamide; I/R, ischemia-reperfusion; SNAP,S-nitroso-N-acetylpenicillamine; SIN-1, 3-morpholinosydnonimine; LDH, lactate dehydrogenase; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; MPP, 1-methyl-4-phenylpyridium; ISQ, 1,5-dihydroisoquinoline; PHT, 6(5H)-phenanthridinone; DPQ, 3,4-dihydro-5-[4-1(1-piperidinyl)buthoxy]-1(2H)-isoquinolinone; OGD, oxygen-glucose deprivation; MCA, middle cerebral artery; H/R, hypoxia-reoxygenation; BCo, bilateral carotid occlusion; PEA, phosphoethanolamine; SAH, subarachnoidal hemorrhage;t-BuOOH, tert-butylhydroperoxide; CCI, chronic constriction injury.