ArticleCNS neuroscience & therapeutics2014
P2X7 receptor inhibition interrupts the progression of seizures in immature rats and reduces hippocampal damage.
Article in CNS neuroscience & therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 62 citations in OpenAlex.
- Review
- Sinomenine ameliorates collagen-induced arthritis in mice by targeting GBP5 and regulating the P2X7 receptor to suppress NLRP3-related signaling pathways.Acta pharmacologica Sinica · 2023Article
- Triggering of Major Brain Disorders by Protons and ATP: The Role of ASICs and P2X Receptors.Neuroscience bulletin · 2023Review
- Microglia and status epilepticus in the immature brain.Epilepsia open · 2023Review
- The P2X7 Receptor as a Mechanistic Biomarker for Epilepsy.International journal of molecular sciences · 2023Review
- MicroRNA: Crucial modulator in purinergic signalling involved diseases.Purinergic signalling · 2023Review
- Quantification of the purinergic P2XJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Seizures in PPT1 Knock-In Mice Are Associated with Inflammatory Activation of Microglia.International journal of molecular sciences · 2022Article
- Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor.International journal of molecular sciences · 2022Review
- P2X7 Receptor Antagonist Reduces Fibrosis and Inflammation in a Mouse Model of Alpha-Sarcoglycan Muscular Dystrophy.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Mesial Temporal Lobe Epilepsy (MTLE) Drug-Refractoriness Is Associated With P2X7 Receptors Overexpression in the Human Hippocampus and Temporal Neocortex and May Be Predicted by Low Circulating Levels of miR-22.Frontiers in cellular neuroscience · 2022Article
- Analyzing the Role of the P2X7 Receptor in Epilepsy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- ATP and adenosine-Two players in the control of seizures and epilepsy development.Progress in neurobiology · 2021Review
- P2XFrontiers in cellular neuroscience · 2021Review
- Targeting Neuroinflammation via Purinergic P2 Receptors for Disease Modification in Drug-Refractory Epilepsy.Journal of inflammation research · 2021Review
- Review
- Neonatal Seizures and Purinergic Signalling.International journal of molecular sciences · 2020Review
- P2X7 Receptors Amplify CNS Damage in Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- The Role of NMDA Receptors in the Effect of Purinergic P2X7 Receptor on Spontaneous Seizure Activity in WAG/Rij Rats With Genetic Absence Epilepsy.Frontiers in neuroscience · 2020Article
- P2X7 Receptor-Dependent microRNA Expression Profile in the Brain Following Status Epilepticus in Mice.Frontiers in molecular neuroscience · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsEarly-life seizures, particularly when prolonged, may be harmful to the brain. Current pharmacotherapy is often ineffective; therefore, novel neuro- and/or glio-transmitter systems should be explored for targeting. The P2X7 receptor is a cation-permeable channel with trophic and excitability effects on neurons and glia which is activated by high amounts of ATP that may be released in the setting of injury after severe seizures. Here, we tested the effects of A-438079, a potent and selective P2X7 receptor antagonist in a lesional model of early-life status epilepticus.
methodsSeizures were induced by intra-amygdala kainic acid in 10-day-old rat pups. Electrographic seizure severity, changes to P2X7 receptor expression, inflammatory responses and histological effects were evaluated.
resultsSeizures induced by intra-amygdala kainic acid increased levels of P2X7 receptor protein and interleukin-1β and caused significant cell death within the ipsilateral hippocampus. A-438079 rapidly reached the brain following systemic injection in P10 rats. Intraperitoneal injection of A-438079 (5 and 15 mg/kg) 60 min after triggering seizures reduced seizure severity and neuronal death within the hippocampus. A-438079 had superior neuroprotective effects compared with an equally seizure-suppressive dose of phenobarbital (25 mg/kg).
conclusionsThese results suggest P2X7 receptor antagonists may be suitable as frontline or adjunctive treatments of pediatric status epilepticus or other early-life seizures, particularly when associated with brain damage.
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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.