ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Diadenosine tetraphosphate protects against injuries induced by ischemia and 6-hydroxydopamine in rat brain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 68 citations in OpenAlex.
- Qishiwei Zhenzhu Pills Protect Against Cerebral Ischemia via the P53/Cytochrome C/Apoptotic Protease Activating Factor 1-Mediated Mitochondrial Apoptosis Pathway.CNS neuroscience & therapeutics · 2025Article
- The Plasma Membrane Purinoreceptor P2K1/DORN1 Is Essential in Stomatal Closure Evoked by Extracellular Diadenosine Tetraphosphate (ApInternational journal of molecular sciences · 2023Article
- Hyperhomocysteinemia Increases Cortical Excitability and Aggravates Mechanical Hyperalgesia and Anxiety in a Nitroglycerine-Induced Migraine Model in Rats.Biomolecules · 2022Article
- Purinergic Signalling in Parkinson's Disease: A Multi-target System to Combat Neurodegeneration.Neurochemical research · 2019Review
- Increased ApPurinergic signalling · 2018Article
- Diadenosine tetraphosphate (ApPurinergic signalling · 2017Article
- The effects of different doses of estradiol (E2) on cerebral ischemia in an in vitro model of oxygen and glucose deprivation and reperfusion and in a rat model of middle carotid artery occlusion.BMC neuroscience · 2013Article
- Early post-treatment with 9-cis retinoic acid reduces neurodegeneration of dopaminergic neurons in a rat model of Parkinson's disease.BMC neuroscience · 2012Article
- Suppression of endogenous PPARγ increases vulnerability to methamphetamine-induced injury in mouse nigrostriatal dopaminergic pathway.Psychopharmacology · 2012Article
- Neurorestoration.Parkinsonism & related disorders · 2012Review
- Targeted over-expression of glutamate transporter 1 (GLT-1) reduces ischemic brain injury in a rat model of stroke.PloS one · 2011Article
- Enhanced survival of dopaminergic neuronal transplants in hemiparkinsonian rats by the p53 inactivator PFT-α.Cell transplantation · 2011Article
- Correlation of locomotor activity and brain infarction in rats with transient focal ischemia.Journal of neuroscience methods · 2010Article
- Oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Alzheimer's disease: many pathways to neurodegeneration.Journal of Alzheimer's disease : JAD · 2010Review
- Mesencephalic astrocyte-derived neurotrophic factor reduces ischemic brain injury and promotes behavioral recovery in rats.The Journal of comparative neurology · 2009Article
- Astaxanthin reduces ischemic brain injury in adult rats.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2009Article
- Delayed treatment with a p53 inhibitor enhances recovery in stroke brain.Annals of neurology · 2009Article
- Diadenosine tetraphosphate reduces toxicity caused by high-dose methamphetamine administration.Neurotoxicology · 2009Article
- 9-Cis-retinoic acid reduces ischemic brain injury in rodents via bone morphogenetic protein.Journal of neuroscience research · 2009Article
- An immortalized rat ventral mesencephalic cell line, RTC4, is protective in a rodent model of stroke.Cell transplantation · 2007Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Diadenosine tetraphosphate (AP4A), an endogenous diadenosine polyphosphate, reduces ischemic injury in the heart. In this study, we report the potent and protective effects of AP4A in rodent models of stroke and Parkinson's disease. AP4A, given intracerebroventricularly before middle cerebral artery (MCA) ligation, reduced cerebral infarction size and enhanced locomotor activity in adult rats. The intravenous administration of AP4A also induced protection when given early after MCA ligation. AP4A suppressed terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) induced by hypoxia/reperfusion in primary cortical cultures, and reduced both ischemia-induced translocation of mitochondrial cytochrome c and the increase in cytoplasmic caspase-3 activity in vivo. The purinergic P2/P4 antagonist di-inosine pentaphosphate or P1-receptor antagonist sulfonylphenyl theophylline, but not the P2-receptor antagonist suramin, antagonized the effect of AP4A, suggesting that the observed protection is mediated through an anti-apoptotic mechanism and the activation of P1- and P4-purinergic receptors. AP4A also afforded protection from toxicity induced by unilateral medial forebrain bundle injection of 6-hydroxydopamine (6-OHDA). One month after lesioning, vehicle-treated rats exhibited amphetamine-induced rotation. Minimal tyrosine hydroxylase immunoreactivity was detected in the lesioned nigra or striatum. No KCl-induced dopamine release was found in the lesioned striatum. All of these indices of dopaminergic degeneration were attenuated by pretreatment with AP4A. In addition, AP4A reduced TUNEL in the lesioned nigra 2 d after 6-OHDA administration. Collectively, our data suggest that AP4A is protective against neuronal injuries induced by ischemia or 6-OHDA through the inhibition of apoptosis. We propose that AP4A may be a potentially useful target molecule in the therapy of stroke and Parkinson's disease.
Indexed as
Identifiers
12944527PMC6740595W2101155625What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.