ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2021
Peripheral Myeloid Cell EP2 Activation Contributes to the Deleterious Consequences of Status Epilepticus.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- Novel EP2 Antagonist Attenuates Microgliosis and Memory Deficits in Pilocarpine-Induced Status Epilepticus Mice.Journal of medicinal chemistry · 2026Article
- Obstructive sleep apnea and seizures: pathophysiological mechanisms and clinical implications: a narrative review.Sleep & breathing = Schlaf & Atmung · 2026Review
- Antagonism of the EP2 Receptor Reveals Sex-Specific Protection in a Two-Hit Mouse Model of Alzheimer's Disease.ACS chemical neuroscience · 2026Article
- Neuroinflammation and Disease: Pathways and Opportunities.Annual review of pharmacology and toxicology · 2026Review
- Brain-invading monocytes promote seizure-associated cognitive deficits and neurodegeneration.Neuropharmacology · 2025Article
- Modulating inflammatory prostaglandin E2 signaling to mitigate neurobehavioral comorbidities associated with seizure disorders.Acta pharmaceutica Sinica. B · 2025Review
- Schwann cell-secreted PGECell · 2024Article
- Phosphoglycerate kinase (PGK) 1 succinylation modulates epileptic seizures and the blood-brain barrier.Experimental animals · 2023Article
- Complementary roles of EP2 and EP4 receptors in malignant glioma.British journal of pharmacology · 2023Article
- Abnormal DNA methylation analysis of leucine-rich glioma-inactivated 1 antibody encephalitis reveals novel methylation-driven genes related to prognostic and clinical features.Clinical epigenetics · 2023Article
- Targeting EP2 Receptor for Drug Discovery: Strengths, Weaknesses, Opportunities, and Threats (SWOT) Analysis.Journal of medicinal chemistry · 2023Review
- Pharmacological inhibition of the inflammatory receptor CCR2 relieves the early deleterious consequences of status epilepticus.Scientific reports · 2023Article
- Neuroinflammatory mediators in acquired epilepsy: an update.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Systemic inflammation as a biomarker of seizure propensity and a target for treatment to reduce seizure propensity.Epilepsia open · 2023Review
- Preclinical development of an EP2 antagonist for post-seizure cognitive deficits.Neuropharmacology · 2023Article
- Temporal Expression of Neuroinflammatory and Oxidative Stress Markers and Prostaglandin E2 Receptor EP2 Antagonist Effect in a Rat Model of Epileptogenesis.ACS pharmacology & translational science · 2023Article
- Neuroinflammation in epileptogenesis: from pathophysiology to therapeutic strategies.Frontiers in immunology · 2023Review
- Second-Generation Prostaglandin Receptor EP2 Antagonist, TG8-260, with High Potency, Selectivity, Oral Bioavailability, and Anti-Inflammatory Properties.ACS pharmacology & translational science · 2022Article
- Distinct Cell-specific Roles of NOX2 and MyD88 in Epileptogenesis.Frontiers in cell and developmental biology · 2022Review
- Sleep Disruption Worsens Seizures: Neuroinflammation as a Potential Mechanistic Link.International journal of molecular sciences · 2021Review
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9 authors at 1 institution in 1 country.
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Abstract
A multidimensional inflammatory response ensues after status epilepticus (SE), driven partly by cyclooxygenase-2-mediated activation of prostaglandin EP2 receptors. The inflammatory response is typified by astrocytosis, microgliosis, erosion of the blood-brain barrier (BBB), formation of inflammatory cytokines, and brain infiltration of blood-borne monocytes. Our previous studies have shown that inhibition of monocyte brain invasion or systemic administration of an EP2 receptor antagonist relieves multiple deleterious consequences of SE. Here we identify those effects of EP2 antagonism that are reproduced by conditional ablation of EP2 receptors in immune myeloid cells and show that systemic EP2 antagonism blocks monocyte brain entry in male mice. The induction of hippocampal IL-6 after pilocarpine SE was nearly abolished in EP2 conditional KO mice. Serum albumin levels in the cortex, a measure of BBB breakdown, were significantly higher after SE in EP2-sufficient mice but not in EP2 conditional KOs. EP2 deficiency in innate immune cells accelerated the recovery from sickness behaviors following SE. Surprisingly, neurodegeneration was not alleviated in myeloid conditional KOs. Systemic EP2 antagonism prevented monocyte brain infiltration and provided broader rescue of SE-induced effects than myeloid EP2 ablation, including neuroprotection and broader suppression of inflammatory mediators. Reporter expression indicated that the cellular target of CD11b-driven Cre was circulating myeloid cells but, unexpectedly, not microglia. These findings indicate that activation of EP2 receptors on immune myeloid cells drives substantial deficits in behavior and disrupts the BBB after SE. The benefits of systemic EP2 antagonism can be attributed, in part, to blocking brain recruitment of blood-borne monocytes.
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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.