Table 3

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

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.