{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:28:13Z","timestamp":1787848093537,"version":"build-2784847793"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001596","name":"Irish Research Council for Science, Engineering and Technology","doi-asserted-by":"publisher","award":["GOIPD\/2020\/865"],"award-info":[{"award-number":["GOIPD\/2020\/865"]}],"id":[{"id":"10.13039\/501100001596","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["16\/RC\/3948"],"award-info":[{"award-number":["16\/RC\/3948"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["17\/CDA\/4708"],"award-info":[{"award-number":["17\/CDA\/4708"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005930","name":"ASCRS Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005930","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The P2X7 receptor (P2X7R) is an important contributor to neuroinflammation, responding to extracellularly released adenosine triphosphate. Expression of the P2X7R is increased in the brain in experimental and human epilepsy, and genetic or pharmacologic targeting of the receptor can reduce seizure frequency and severity in preclinical models. Experimentally induced seizures also increase levels of the P2X7R in blood. Here, we tested <jats:sup>18<\/jats:sup>F\u2010JNJ\u201064413739, a positron emission tomography (PET) P2X7R antagonist, as a potential noninvasive biomarker of seizure\u2010damage and epileptogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Status epilepticus was induced via an intra\u2010amygdala microinjection of kainic acid. Static PET studies (30\u2009min duration, initiated 30\u2009min after tracer administration) were conducted 48\u2009h after status epilepticus via an intravenous injection of <jats:sup>18<\/jats:sup>F\u2010JNJ\u201064413739. PET images were coregistered with a brain magnetic resonance imaging atlas, tracer uptake was determined in the different brain regions and peripheral organs, and values were correlated to seizure severity during status epilepticus. <jats:sup>18<\/jats:sup>F\u2010JNJ\u201064413739 was also applied to ex vivo human brain slices obtained following surgical resection for intractable temporal lobe epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>P2X7R radiotracer uptake correlated strongly with seizure severity during status epilepticus in brain structures including the cerebellum and ipsi\u2010 and contralateral cortex, hippocampus, striatum, and thalamus. In addition, a correlation between radiotracer uptake and seizure severity was also evident in peripheral organs such as the heart and the liver. Finally, P2X7R radiotracer uptake was found elevated in brain sections from patients with temporal lobe epilepsy when compared to control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Taken together, our data suggest that P2X7R\u2010based PET imaging may help to identify seizure\u2010induced neuropathology and temporal lobe epilepsy patients with increased P2X7R levels possibly benefitting from P2X7R\u2010based treatments.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17484","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T14:14:59Z","timestamp":1670854499000},"page":"511-523","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Increased uptake of the <scp>P2X7<\/scp> receptor radiotracer <scp><sup>18<\/sup>F\u2010JNJ<\/scp>\u201064413739 in the brain and peripheral organs according to the severity of status epilepticus in male mice"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7833-3863","authenticated-orcid":false,"given":"James","family":"Morgan","sequence":"first","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences  Dublin Ireland"},{"name":"Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine, and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Moreno","sequence":"additional","affiliation":[{"name":"CIC biomaGUNE Basque Research and Technology Alliance (BRTA)  San Sebastian Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuri\u00f1e","family":"Baz","sequence":"additional","affiliation":[{"name":"CIC biomaGUNE Basque Research and Technology Alliance (BRTA)  San Sebastian Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Men\u00e9ndez M\u00e9ndez","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Leister","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hygiene Philipps University  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciara","family":"Melia","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathon","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences  Dublin Ireland"},{"name":"FutureNeuro, Science Foundation Ireland (SFI) Research Centre for Chronic and Rare Neurological Diseases, Royal College of Surgeons in Ireland University of Medicine and Health Sciences  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Visekruna","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hygiene Philipps University  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Nicke","sequence":"additional","affiliation":[{"name":"Walther Straub Institute of Pharmacology and Toxicology Ludwig Maximilian University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anindya","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Neuroimmunology Discover, Neuroscience, Janssen Research and Development  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Ceusters","sequence":"additional","affiliation":[{"name":"Neuroscience Therapeutic Area, Janssen Research and Development, Janssen Pharmaceutica  Beerse Belgium"},{"name":"Marc Ceusters Company  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6237-9632","authenticated-orcid":false,"given":"David C.","family":"Henshall","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences  Dublin Ireland"},{"name":"FutureNeuro, Science Foundation Ireland (SFI) Research Centre for Chronic and Rare Neurological Diseases, Royal College of Surgeons in Ireland University of Medicine and Health Sciences  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"G\u00f3mez\u2010Vallejo","sequence":"additional","affiliation":[{"name":"CIC biomaGUNE Basque Research and Technology Alliance (BRTA)  San Sebastian Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0821-9838","authenticated-orcid":false,"given":"Jordi","family":"Llop","sequence":"additional","affiliation":[{"name":"CIC biomaGUNE Basque Research and Technology Alliance (BRTA)  San Sebastian Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9137-0637","authenticated-orcid":false,"given":"Tobias","family":"Engel","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and 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