{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:13:45Z","timestamp":1790324025542,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["1024032700128\u20108\u20101.6.4"],"award-info":[{"award-number":["1024032700128\u20108\u20101.6.4"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hyperexcitation of neuronal networks is a key mechanism underlying excitotoxic neuronal death in conditions such as epilepsy, ischemic stroke, and traumatic brain injury. Given the inhibitory role of G\n                    <jats:sub>i<\/jats:sub>\n                    \u2010coupled receptors, A\n                    <jats:sub>1<\/jats:sub>\n                    adenosine receptors (A\n                    <jats:sub>1<\/jats:sub>\n                    Rs) represent promising targets for neuroprotective and anticonvulsant therapy. In this study, we investigated the effects of A\n                    <jats:sub>1<\/jats:sub>\n                    R agonists (CCPA and N\n                    <jats:sup>6<\/jats:sup>\n                    \u2010CHA) and positive allosteric modulators (PAMs; PD81723 and VCP171) using in\u00a0vitro models of hyperexcitation (glutamate excitotoxicity, NH\n                    <jats:sub>4<\/jats:sub>\n                    Cl\u2010induced hyperexcitation and bicuculline\u2010induced epileptiform activity) and an in\u00a0vivo picrotoxin\u2010induced seizure model in mice. Calcium imaging, electrophysiology, and pharmacological inhibition were used to assess underlying mechanisms. A\n                    <jats:sub>1<\/jats:sub>\n                    R agonists suppressed hyperexcitation in all in\u00a0vitro models and reduced seizure severity and mortality in\u00a0vivo. In hippocampal neuron\u2013glial cultures, these effects were mediated by activation of both neuronal and astrocytic A\n                    <jats:sub>1<\/jats:sub>\n                    Rs. In astrocytes, A\n                    <jats:sub>1<\/jats:sub>\n                    R activation induced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients and promoted GABA release, with pharmacological evidence supporting the involvement of G\u03b2\u03b3 subunits, phospholipase C, and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent protein kinase C. PAMs also suppressed hyperexcitation in\u00a0vitro; however, only chronic administration of VCP171 produced significant anticonvulsant effects in\u00a0vivo, while acute treatment was ineffective. In conclusion, A\n                    <jats:sub>1<\/jats:sub>\n                    R\u2010mediated suppression of hyperexcitation involves both neuronal and astrocytic mechanisms, including astrocyte\u2010dependent GABA release. A\n                    <jats:sub>1<\/jats:sub>\n                    adenosine receptors represent a promising therapeutic target, and their PAMs may provide therapeutic potential.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70556-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70556","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:45:31Z","timestamp":1790073931000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Action of Agonists and Modulators of\n                    <scp>\n                      A\n                      <sub>1<\/sub>\n                    <\/scp>\n                    Adenosine Receptors Upon Hyperexcitation: Mechanism of the Antiepileptic Activity and Role of Neuron\u2010Glial Interaction"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8350-6301","authenticated-orcid":false,"given":"Polina E.","family":"Ryazantseva","sequence":"first","affiliation":[{"name":"Federal Research Center \u201cPushchino Scientific Center for Biological Research of the Russian Academy of Sciences\u201d Institute of Cell Biophysics of the Russian Academy of Sciences  Pushchino Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4221-5344","authenticated-orcid":false,"given":"Sergei G.","family":"Gaidin","sequence":"additional","affiliation":[{"name":"Federal Research Center \u201cPushchino Scientific Center for Biological Research of the Russian Academy of Sciences\u201d Institute of Cell Biophysics of the Russian Academy of Sciences  Pushchino Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0673-0998","authenticated-orcid":false,"given":"Sergei A.","family":"Maiorov","sequence":"additional","affiliation":[{"name":"Federal Research Center \u201cPushchino Scientific Center for Biological Research of the Russian Academy of Sciences\u201d Institute of Cell Biophysics of the Russian Academy of Sciences  Pushchino Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis P.","family":"Laryushkin","sequence":"additional","affiliation":[{"name":"Federal Research Center \u201cPushchino Scientific Center for Biological Research of the Russian Academy of Sciences\u201d Institute of Cell Biophysics of the Russian Academy of Sciences  Pushchino Russian 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