{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T16:21:24Z","timestamp":1780676484537,"version":"3.54.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondations Gueules cass\u00e9es","award":["FGC 57-2020"],"award-info":[{"award-number":["FGC 57-2020"]}]},{"name":"CNRS","award":["UMR5292"],"award-info":[{"award-number":["UMR5292"]}]},{"name":"University of Szeged Open Access Fund","award":["8237"],"award-info":[{"award-number":["8237"]}]},{"name":"Ministry of Innovation and Technology of Hungary and the National Research, Development and Innovation Fund","award":["TKP2021-EGA-28"],"award-info":[{"award-number":["TKP2021-EGA-28"]}]},{"DOI":"10.13039\/501100011019","name":"National Research, Development and Innovation Office of Hungary","doi-asserted-by":"crossref","award":["FK142218"],"award-info":[{"award-number":["FK142218"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011019","name":"National Research, Development and Innovation Office of Hungary","doi-asserted-by":"crossref","award":["K146725"],"award-info":[{"award-number":["K146725"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011019","name":"National Research, Development and Innovation Office of Hungary","doi-asserted-by":"crossref","award":["150356"],"award-info":[{"award-number":["150356"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"crossref"}]},{"name":"EU\u2019s Horizon 2020 research and innovation program","award":["739593"],"award-info":[{"award-number":["739593"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cerebral edema is a hallmark of lesion progression after acute ischemic stroke (AIS) and a major contributor to the evolution of spreading depolarizations (SDs). SDs trigger extracellular glutamate accumulation and excitotoxic injury, yet the mechanisms linking edema formation, glutamate dysregulation, and SD dynamics remain incompletely understood. Here, we investigated how inhibiting glial swelling and volume-regulated glutamate release, or blocking neuronal ionotropic glutamate receptors alters SD features under hypo-osmotic stress in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Acute 350-\u00b5m-thick brain slices were prepared from male Wistar rats (n = 24). Edema was induced using hypoosmotic medium (130\u219260 mM NaCl), and SD was triggered by hypoxia. SD evolution and extracellular glutamate levels were monitored using local field potential recordings, intrinsic optical signal imaging, and enzyme-based glutamate biosensors. Astrocyte swelling was reduced by blocking AQP4+NKCC1 (TGN-020 + bumetanide) and VRAC channels (DCPIB), while neuronal NMDA and AMPA\/kainate receptors were antagonized with MK-801 + CNQX.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Inhibition of AQP4, NKCC1, or VRAC channels restricted the cortical area invaded by SD, shortened SD duration, and reduced extracellular glutamate accumulation. In contrast, blockade of NMDA or AMPA\/kainate receptors markedly decreased SD propagation and glutamate buildup. Both astrocytic and neuronal interventions disrupted typical SD initiation patterns, producing atypical, multifocal SD events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate that astrocyte volume regulation and neuronal ionotropic glutamate receptors jointly shape SD characteristics under osmotic stress, identifying astrocytic water\/ion homeostasis and glutamatergic signaling as potential therapeutic targets to limit excitotoxic injury in acute cerebrovascular disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fncel.2025.1722194","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:35:31Z","timestamp":1768973731000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Glutamate load fosters spreading depolarization under osmotic stress in brain slices"],"prefix":"10.3389","volume":"19","author":[{"given":"Rita","family":"Frank","sequence":"first","affiliation":[{"name":"Hungarian Centre of Excellence for Molecular Medicine, University of Szeged Cerebral Blood Flow and Metabolism Research Group","place":["Szeged, Hungary"]},{"name":"Department of Cell Biology and Molecular Medicine, Albert Szent-Gy\u00f6rgyi Medical School and Faculty of Science and Informatics, University of Szeged","place":["Szeged, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Marinesco","sequence":"additional","affiliation":[{"name":"Lyon Neuroscience Research Center, Inserm U1028, CNRS UMR, University Claude Bernard Lyon I","place":["Lyon, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Bari","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Informatics, Albert Szent-Gy\u00f6rgyi Medical School and Faculty of Science and Informatics, University of Szeged","place":["Szeged, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1kos","family":"Menyh\u00e1rt","sequence":"additional","affiliation":[{"name":"Hungarian Centre of Excellence for Molecular Medicine, University of Szeged Cerebral Blood Flow and Metabolism Research Group","place":["Szeged, Hungary"]},{"name":"Department of Cell Biology and Molecular Medicine, Albert Szent-Gy\u00f6rgyi Medical School and Faculty of Science and Informatics, University of Szeged","place":["Szeged, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Farkas","sequence":"additional","affiliation":[{"name":"Hungarian Centre of Excellence for Molecular Medicine, University of Szeged Cerebral Blood Flow and Metabolism Research Group","place":["Szeged, Hungary"]},{"name":"Department of Cell Biology and Molecular Medicine, Albert Szent-Gy\u00f6rgyi Medical School and Faculty of Science and Informatics, University of Szeged","place":["Szeged, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2108","DOI":"10.1002\/glia.24241","article-title":"Novel mechanism of hypoxic neuronal injury mediated by non-excitatory amino acids and astroglial swelling","volume":"70","author":"Alvarez-Merz","year":"2022","journal-title":"Glia"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s12028-021-01429-4","article-title":"Questioning glutamate excitotoxicity in acute brain damage: the importance of spreading depolarization","volume":"37","author":"Andrew","year":"2022","journal-title":"Neurocrit. 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