{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T12:54:01Z","timestamp":1784120041252,"version":"3.55.0"},"reference-count":96,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1NS083858"],"award-info":[{"award-number":["RO1NS083858"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In ischemic stroke and post\u2010traumatic brain injury (TBI), blood\u2013brain barrier disruption leads to leaking plasma amino acids (AA) into cerebral parenchyma. Bleeding in hemorrhagic stroke and TBI also release plasma AA. Although excitotoxic AA were extensively studied, little is known about non\u2010excitatory AA during hypoxic injury. Hypoxia\u2010induced synaptic depression in hippocampal slices becomes irreversible with non\u2010excitatory AA, alongside their intracellular accumulation and increased tissue electrical resistance. Four non\u2010excitatory AA (\n                    <jats:sc>l<\/jats:sc>\n                    \u2010alanine, glycine,\n                    <jats:sc>l<\/jats:sc>\n                    \u2010glutamine,\n                    <jats:sc>l<\/jats:sc>\n                    \u2010serine: AGQS) at plasmatic concentrations were applied to slices from mice expressing EGFP in pyramidal neurons or astrocytes during normoxia or hypoxia. Two\u2010photon imaging, light transmittance (LT) changes, and electrophysiological field recordings followed by electron microscopy in hippocampal CA1 st. radiatum were used to monitor synaptic function concurrently with cellular swelling and injury. During normoxia, AGQS\u2010induced increase in LT was due to astroglial but not neuronal swelling. LT raise during hypoxia and AGQS manifested astroglial and neuronal swelling accompanied by a permanent loss of synaptic transmission and irreversible dendritic beading, signifying acute damage. Neuronal injury was not triggered by spreading depolarization which did not occur in our experiments. Hypoxia without AGQS did not cause cell swelling, leaving dendrites intact. Inhibition of NMDA receptors prevented neuronal damage and irreversible loss of synaptic function. Deleterious effects of AGQS during hypoxia were prevented by alanine\u2010serine\u2010cysteine transporters (ASCT2) and volume\u2010regulated anion channels (VRAC) blockers. Our findings suggest that astroglial swelling induced by accumulation of non\u2010excitatory AA and release of excitotoxins through antiporters and VRAC may exacerbate the hypoxia\u2010induced neuronal injury.\n                  <\/jats:p>","DOI":"10.1002\/glia.24241","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T10:29:37Z","timestamp":1657276177000},"page":"2108-2130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Novel mechanism of hypoxic neuronal injury mediated by non\u2010excitatory amino acids and astroglial swelling"],"prefix":"10.1002","volume":"70","author":[{"given":"Iris","family":"\u00c1lvarez\u2010Merz","sequence":"first","affiliation":[{"name":"Department de Farmacolog\u00eda y Terap\u00e9utica, ITH, Facultad de Medicina Universidad Aut\u00f3noma de Madrid, IRYCIS Madrid Spain"},{"name":"Servicio de Neurobiolog\u00eda\u2010Investigaci\u00f3n Hospital Universitario Ram\u00f3n y Cajal, IRYCIS Madrid Spain"},{"name":"Department of Neuroscience and Regenerative Medicine Medical College of Georgia at Augusta University Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioulia V.","family":"Fomitcheva","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Medical College of Georgia at Augusta University Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Sword","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Regenerative Medicine Medical College of Georgia at Augusta University Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas M.","family":"Hern\u00e1ndez\u2010Guijo","sequence":"additional","affiliation":[{"name":"Department de Farmacolog\u00eda y Terap\u00e9utica, ITH, Facultad de Medicina Universidad Aut\u00f3noma de Madrid, IRYCIS Madrid 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