{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T03:44:01Z","timestamp":1768535041514,"version":"3.49.0"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T00:00:00Z","timestamp":1398038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Early\u2010life seizures, particularly when prolonged, may be harmful to the brain. Current pharmacotherapy is often ineffective; therefore, novel neuro\u2010 and\/or glio\u2010transmitter systems should be explored for targeting. The P2X7 receptor is a cation\u2010permeable channel with trophic and excitability effects on neurons and glia which is activated by high amounts of <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> that may be released in the setting of injury after severe seizures. Here, we tested the effects of A\u2010438079, a potent and selective P2X7 receptor antagonist in a lesional model of early\u2010life status epilepticus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seizures were induced by intra\u2010amygdala kainic acid in 10\u2010day\u2010old rat pups. Electrographic seizure severity, changes to P2X7 receptor expression, inflammatory responses and histological effects were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seizures induced by intra\u2010amygdala kainic acid increased levels of P2X7 receptor protein and interleukin\u20101<jats:italic>\u03b2<\/jats:italic> and caused significant cell death within the ipsilateral hippocampus. A\u2010438079 rapidly reached the brain following systemic injection in P10 rats. Intraperitoneal injection of A\u2010438079 (5 and 15\u00a0mg\/kg) 60\u00a0min after triggering seizures reduced seizure severity and neuronal death within the hippocampus. A\u2010438079 had superior neuroprotective effects compared with an equally seizure\u2010suppressive dose of phenobarbital (25\u00a0mg\/kg).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest P2X7 receptor antagonists may be suitable as frontline or adjunctive treatments of pediatric status epilepticus or other early\u2010life seizures, particularly when associated with brain damage.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12272","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T08:40:39Z","timestamp":1398069639000},"page":"556-564","source":"Crossref","is-referenced-by-count":57,"title":["P2X7 Receptor Inhibition Interrupts the Progression of Seizures in Immature Rats and Reduces Hippocampal Damage"],"prefix":"10.1111","volume":"20","author":[{"given":"Guillaume","family":"Mesuret","sequence":"first","affiliation":[{"name":"Department of Physiology &amp; Medical Physics Royal College of Surgeons in Ireland Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Engel","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Medical Physics Royal College of Surgeons in Ireland Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen V.","family":"Hessel","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology Brain Center Rudolf Magnus University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amaya","family":"Sanz\u2010Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Medical Physics Royal College of Surgeons in Ireland Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba","family":"Jimenez\u2010Pacheco","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Medical Physics Royal College of Surgeons in Ireland Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Teresa","family":"Miras\u2010Portugal","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology IV. Veterinary Faculty Complutense University of Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Diaz\u2010Hernandez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology IV. Veterinary Faculty Complutense University of Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Henshall","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Medical Physics Royal College of Surgeons in Ireland Dublin Ireland"},{"name":"Irish Centre for Fetal and Neonatal Translational Research (INFANT) Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,4,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21167"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2010.06.010"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70141-8"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(04)00881-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02943.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200110000-00005"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.03.040"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-011-0148-3"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2012.08140.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2013.01.001"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(06)70374-X"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2605"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.003129"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-14-05938.2002"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00920.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-04-01320.2003"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200410250-00017"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e32833d9142"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5512-08.2009"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22302"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.209452"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0579-07.2007"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2006.03.007"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-138883"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-196089"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12257"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44818"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00237"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.03.035"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090119"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01069.x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3295-09.2010"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21593"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057148"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn920"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1301"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2013.04.005"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006781200"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.11.064"},{"key":"e_1_2_7_41_1","first-page":"174","article-title":"P2X7 receptor in epilepsy; role in pathophysiology and potential targeting for seizure control","volume":"4","author":"Engel T","year":"2012","journal-title":"Int J Physiol Pathophysiol Pharmacol"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.3.579"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-08-03061.2002"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20358"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.178"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1082"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05387.x"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-122275"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410360314"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2009.09.019"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2012.00120"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03391.x"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12314"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(02)00164-3"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcns.12272","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.12272","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T23:00:38Z","timestamp":1695510038000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.12272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,21]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["10.1111\/cns.12272"],"URL":"https:\/\/doi.org\/10.1111\/cns.12272","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,21]]}}}