Experimental Model | Inducer of Injury | Mode of PARP Inhibition | Effect of PARP Inhibition | Reference |
---|---|---|---|---|
Rat hippocampal neurons | Nitric oxide | 3-AB, nicam | Improved neuronal conductance | Wallis et al., 1993 |
Rat cortical cultures | NMDA, SNAP | Benzamide, 3-AB, ISQ | Reduced cell death | Zhang et al., 1994 |
Cerebellar granule cells | Glutamate | Benzamide, 3-AB, 3-APH | Reduced cell death | Cosi et al., 1994 |
Rat cortical cultures | NMDA, SNAP, SIN-1 | PARP−/−phenotype, benzamide, DHQ | Reduced cell death | Eliasson et al., 1997 |
NSC39 spinal cord line | Peroxynitrite, H2O2 | Benzamide, nicam, 3-AB, PHT | Reduced cell death | Cookson et al., 1998 |
Cerebellar granule neurons | 3-Acetylpyridine | 3-AB | Protection against cell death | Wullner et al., 1997 |
Rat cortex | H2O2 | Benzamide, nicam | Reduced cell death | Hivert et al., 1998 |
C6 astrocytoma cells | Peroxynitrite | INH2BP | Reduced cell death | Endres et al., 1998b |
Rat motoneurons | OGD | 3-methoxybenzamide | Reduction of ATP depletion | Tasker et al., 1998 |
Rat hippocampal neurons | Homocysteine | 3-AB | Reduction of NAD depletion and cell necrosis | Kruman et al., 2000 |
Rat hippocampal neurons | SIN-1, NOC-9 | Nicam | Reduction of cell necrosis and apoptosis | Lin et al., 2000 |
Mouse neurons and astrocytes | H2O2, NMDA, MNNG | Benzamide, PARG inhibitors gallotannin and nobotanin B | Reduction of cell necrosis | Ying and Swanson, 2000; Ying et al., 2001 |
Mixed rat cortical cells | OGD | Benzamide, PHT, DPQ | Reduction of cell necrosis | Moroni et al., 2001 |
Mixed rat cortical cells | OGD | PJ34 | Reduction of cell necrosis | Abdelkarim et al., 2001 |
Hippocampal slices | OGD | Benzamide, PHT, DPB | No effect on apoptotic death | Moroni et al., 2001 |
Hippocampal slices | Fluid percussion injury | 3-AB | Improved neuronal conductance | Wallis et al., 1996 |
Rat cortical slices | H/R | Benzamide, 3-AB, ISQ | Reduced LDH leakage | Oka et al., 2000 |
Human A72 glioma | H2O2 | 3-AB | Reduced cell death, maintained ATP | Lee et al., 2001 |
Mouse BV-2 microglia mouse hippocampal cultures | NMDA | PARP−/−phenotype | Amelioration of glial migration and of secondary neuronal injury | Ullrich et al., 2001b |
Mouse | MCAo I/R | PARP−/− phenotype, 3-AB | Reduced 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 |
Rat | MCAo, BCo, I/R | DPQ | Reduced infarct size, improved neurological status; at high doses DPQ loses protective effect | Takahashi et al., 1997, 1999 |
Rat | MCAo I/R | 3-AB | Reduced infarct size, attenuation in glutamate and PEA release | Lo et al., 1998 |
Rat | MCAo | 3-AB | Reduced infarct size | Tokime et al., 1998 |
Mouse | MCAo, I/R | INH2BP | Reduced infarct size, improved neurological status | Endres et al., 1998b |
Rat | MCAo I/R | 3-AB, nicam | Reduced infarct size, improved neurological status; at high doses nicam becomes detrimental | Sun and Cheng, 1998 |
Neonatal rat | MCAo I/R | 3-AB | Reduced 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, rat | MCAo I/R | PJ34 | Reduced infarct size, improved neurological status | Abdelkarim et al., 2001 |
Rat | MCAo | PJ34 | Reduced infarct at 4 h permanent MCAo | Abdelkarim et al., 2001 |
Rat | Global brain ischemia | 3-AB | Reduced infarct, improved cortical NAD and phosphocreatine levels, no change in ATP | Plaschke et al., 2000a |
Rat | MCAo I/R | 3-AB | Long-term (28 days) improvement in neurological status and reduced infarct volume | Ding et al., 2001 |
Rat | MCAo | Nicam | Reduced 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 |
Mouse | Cortical trauma | PARP−/− phenotype | Improved neurological function | Whalen et al., 1999 |
Rat | Cortical trauma | GPI 6150 | Reduced lesion size, protection from cell death | LaPlaca et al., 2001 |
Mouse | Intrastriatal NMDA | PARP−/− phenotype | Protection from cell death | Mandir et al., 2000 |
Mouse | intrastriatal AMPA | PARP−/− phenotype | No protection from cell death | Mandir et al., 2000 |
Mouse | t-BuOOH (i.c.v.) | Nicam | Maintenance of NAD, NADP, and NADPH levels in many brain regions | Klaidman et al., 1996, 2001 |
Gerbil | Short BCo | Benzamide, PHT, DPB-ISQ | No effect on hippocampal apoptotic death | Moroni et al., 2001 |
Rat | Short global ischemia and hypothermia | 3-AB | Enhancement of CA1 hippocampal apoptotic death | Nagayama et al., 2000 |
Mouse | Monocular deprivation | PARP−/− phenotype | Protection from cell death in dLGN | Nucci et al., 2001 |
Rat | CCI | Benzamide | Reduced neuronal death, reduced hyperalgesia and mechano-allodynia | Mao et al., 1997 |
Rat | Soman | Benzamide | Reduction in neuronal deficit, improved survival | Meier et al., 1999 |
Mouse | MPTP | PARP−/− phenotype | Reduced cell death, improved function, protection against dopamine loss | Mandir et al., 1999 |
Mouse | MPTP | Benzamide, ISQ | Maintained striatal NAD and ATP protection against dopamine loss | Cosi et al., 1996; Cosi and Marien, 1999 |
Rat | MPP(+) | 3-AB | No protection against the impairment of neuronal dopamine transporter activity | Barc et al., 2001 |
Mouse | Nigral grafting | PARP−/− phenotype | No improvements in implanted cell survival or graft recipient status | Kaminski et al., 1999 |
Guinea pig | I/R of the cochlea | 3-AB | Improved neuronal conductance | Tabuchi et al., 2001 |
Rat | I/R of the retina | 3-AB | Reduced cell death | Lam, 1997; Chiang and Lam, 2000 |
Newborn piglet | E. coli meningitis | 3-AB | Decrease in lactate production, neutrophil infiltration, TNF production, peroxidation and ATP depletion | Park et al., 2001 |
Mouse, rat | E. coli meningitis | 3-AB, PARP−/− phenotype | Decrease in inflammatory mediator production, improved survival and CNS function | Koedel et al., 2002 |
Rabbit | SAH | 3-AB | Attenuated 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.