{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T22:11:12Z","timestamp":1785017472043,"version":"3.55.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T00:00:00Z","timestamp":1612915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Ginkgolide B (GB), a terpene lactone and active ingredient of <jats:italic>Ginkgo biloba<\/jats:italic>, shows protective effects in neuronal cells subjected to hypoxia. We investigated whether GB might protect neurons from hypoxic injury through regulation of neuronal Ca<jats:sup>2+<\/jats:sup> homeostasis. Primary hippocampal neurons subjected to chemical hypoxia (0.7 mM CoCl<jats:sub>2<\/jats:sub>) <jats:italic>in vitro<\/jats:italic> exhibited an increase in cytoplasmic Ca<jats:sup>2+<\/jats:sup> (measured from the fluorescence of fluo-4), but this effect was significantly diminished by pre-treatment with 0.4 mM GB. Electrophysiological recordings from the brain slices of rats exposed to hypoxia <jats:italic>in vivo<\/jats:italic> revealed increases in spontaneous discharge frequency, action potential frequency and calcium current magnitude, and all these effects of hypoxia were suppressed by pre-treatment with 12 mg\/kg GB. Western blot analysis demonstrated that hypoxia was associated with enhanced mRNA and protein expressions of Ca<jats:sub>v<\/jats:sub>1.2 (a voltage-gated Ca<jats:sup>2+<\/jats:sup> channel), STIM1 (a regulator of store-operated Ca<jats:sup>2+<\/jats:sup> entry) and RyR2 (isoforms of Ryanodine Receptor which mediates sarcoplasmic reticulum Ca<jats:sup>2+<\/jats:sup> release), and these actions of hypoxia were suppressed by GB. Taken together, our <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> data suggest that GB might protect neurons from hypoxia, in part, by regulating Ca<jats:sup>2+<\/jats:sup> influx and intracellular Ca<jats:sup>2+<\/jats:sup> release to maintain Ca<jats:sup>2+<\/jats:sup> homeostasis.<\/jats:p>","DOI":"10.3389\/fncel.2020.627846","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T15:59:46Z","timestamp":1612972786000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Ginkgolide B Maintains Calcium Homeostasis in Hypoxic Hippocampal Neurons by Inhibiting Calcium Influx and Intracellular Calcium Release"],"prefix":"10.3389","volume":"14","author":[{"given":"Li","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WenJuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JiHua","family":"Ran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"QingHai","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JianFeng","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/S0092-8674(03)01017-1","article-title":"A key role for TRPM7 channels in anoxic neuronal death","volume":"115","author":"Aarts","year":"2003","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1152\/physrev.1999.79.3.763","article-title":"Sodium\/calcium exchange: its physiological implications","volume":"79","author":"Blaustein","year":"1999","journal-title":"Physiol. 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