ArticleBritish journal of pharmacology2010
Microsomal prostaglandin E synthase-1 contributes to ischaemic excitotoxicity through prostaglandin E2 EP3 receptors.
Article in British journal of pharmacology, 2010. 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, 39 citations in OpenAlex.
- Update on the pathological roles of prostaglandin ETranslational neurodegeneration · 2023Review
- The inducible prostaglandin E synthase (mPGES-1) in neuroinflammatory disorders.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Inhibition of rat locus coeruleus neurons by prostaglandin EFrontiers in pharmacology · 2023Article
- COX-2/PGE2 Pathway Inhibits the Ferroptosis Induced by Cerebral Ischemia Reperfusion.Molecular neurobiology · 2022Article
- miR-204-5p is sponged by TUG1 to aggravate neuron damage induced by focal cerebral ischemia and reperfusion injury through upregulating COX2.Cell death discovery · 2022Article
- Inducible Prostaglandin E Synthase as a Pharmacological Target for Ischemic Stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Small molecules targeting cyclooxygenase/prostanoid cascade in experimental brain ischemia: Do they translate?Medicinal research reviews · 2021Review
- Prostaglandin E receptors as targets for ischemic stroke: Novel evidence and molecular mechanisms of efficacy.Pharmacological research · 2021Review
- Pre- and Neonatal Exposure to Lead (Pb) Induces Neuroinflammation in the Forebrain Cortex, Hippocampus and Cerebellum of Rat Pups.International journal of molecular sciences · 2020Article
- The protection of meloxicam against chronic aluminium overload-induced liver injury in rats.Oncotarget · 2017Article
- Increased Expression of 15-Hydroxyprostaglandin Dehydrogenase in Spinal Astrocytes During Disease Progression in a Model of Amyotrophic Lateral Sclerosis.Cellular and molecular neurobiology · 2017Article
- Contribution of prostanoid signaling to the evolution of spreading depolarization and the associated cerebral blood flow response.Scientific reports · 2016Article
- Organotypic Hippocampal Slices as Models for Stroke and Traumatic Brain Injury.Molecular neurobiology · 2016Review
- Inhibition of prostaglandin E2 receptor EP3 mitigates thrombin-induced brain injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2016Article
- An EP2 Agonist Facilitates NMDA-Induced Outward Currents and Inhibits Dendritic Beading through Activation of BK Channels in Mouse Cortical Neurons.Mediators of inflammation · 2016Article
- Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling Imbalance in Aluminum-Overload Rats.Current Alzheimer research · 2016Article
- Genetic deletion of the prostaglandin E2 E prostanoid receptor subtype 3 improves anatomical and functional outcomes after intracerebral hemorrhage.The European journal of neuroscience · 2015Article
- Hippocampal neuronal cyclooxygenase-2 downstream signaling imbalance in a rat model of chronic aluminium gluconate administration.Behavioral and brain functions : BBF · 2015Article
- Inflammation modulates expression of laminin in the central nervous system following ischemic injury.Journal of neuroinflammation · 2012Article
- Putative role of prostaglandin receptor in intracerebral hemorrhage.Frontiers in neurology · 2012Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeAlthough microsomal prostaglandin E synthase (mPGES)-1 is known to contribute to stroke injury, the underlying mechanisms remain poorly understood. This study examines the hypothesis that EP(3) receptors contribute to stroke injury as downstream effectors of mPGES-1 neurotoxicity through Rho kinase activation. EXPERIMENTAL APPROACH: We used a glutamate-induced excitotoxicity model in cultured rat and mouse hippocampal slices and a mouse middle cerebral artery occlusion-reperfusion model. Effects of an EP(3) receptor antagonist on neuronal damage in mPGES-1 knockout (KO) mice was compared with that in wild-type (WT) mice. KEY
resultsIn cultures of rat hippocampal slices, the mRNAs of EP(1-4) receptors were constitutively expressed and only the EP(3) receptor antagonist ONO-AE3-240 attenuated and only the EP(3) receptor agonist ONO-AE-248 augmented glutamate-induced excitotoxicity in CA1 neurons. Hippocampal slices from mPGES-1 KO mice showed less excitotoxicity than those from WT mice and the EP(3) receptor antagonist did not attenuate the excitotoxicity. In transient focal ischaemia models, injection (i.p.) of an EP(3) antagonist reduced infarction, oedema and neurological dysfunction in WT mice, but not in mPGES-1 KO mice, which showed less injury than WT mice. EP(3) receptor agonist-induced augmentation of excitotoxicity in vitro was ameliorated by the Rho kinase inhibitor Y-27632 and Pertussis toxin. The Rho kinase inhibitor HA-1077 also ameliorated stroke injury in vivo. CONCLUSION AND IMPLICATIONS: Activity of mPGES-1 exacerbated stroke injury through EP(3) receptors and activation of Rho kinase and/or G(i). Thus, mPGES-1 and EP(3) receptors may be valuable therapeutic targets for treatment of human stroke.
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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.