{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:33:47Z","timestamp":1788518027387,"version":"build-2803163510"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000006","name":"Office of Naval Research","doi-asserted-by":"publisher","award":["N00014-18-1-2702"],"award-info":[{"award-number":["N00014-18-1-2702"]}],"id":[{"id":"10.13039\/100000006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-25-00539"],"award-info":[{"award-number":["22-25-00539"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 HL160494-01"],"award-info":[{"award-number":["T32 HL160494-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Oxygen breathing at elevated partial pressures (PO<jats:sub>2<\/jats:sub>\u2019s) at or more than 3 atmospheres absolute (ATA) causes a reduction in brain \u03b3-aminobutyric acid (GABA) levels that impacts the development of central nervous system oxygen toxicity (CNS-OT). Drugs that increase brain GABA content delay the onset of CNS-OT, but it is unknown if oxidant damage is lessened because brain tissue PO<jats:sub>2<\/jats:sub> remains elevated during hyperbaric oxygen (HBO<jats:sub>2<\/jats:sub>) exposures. Experiments were performed in rats and mice to measure brain GABA levels with or without GABA transporter inhibitors (GATs) and its influence on cerebral blood flow, oxidant damage, and aspects of mitochondrial quality control signaling (mitophagy and biogenesis). In rats pretreated with tiagabine (GAT1 inhibitor), the tachycardia, secondary rise in mean arterial blood pressure, and cerebral hyperemia were prevented during HBO<jats:sub>2<\/jats:sub> at 5 and 6 ATA. Tiagabine and the nonselective GAT inhibitor nipecotic acid similarly extended HBO<jats:sub>2<\/jats:sub> seizure latencies. In mice pretreated with tiagabine and exposed to HBO<jats:sub>2<\/jats:sub> at 5 ATA, nuclear and mitochondrial DNA oxidation and astrocytosis was attenuated in the cerebellum and hippocampus. Less oxidant injury in these regions was accompanied by reduced conjugated microtubule-associated protein 1A\/1B-light chain 3 (LC3-II), an index of mitophagy, and phosphorylated cAMP response element binding protein (pCREB), an initiator of mitochondrial biogenesis. We conclude that GABA prevents cerebral hyperemia and delays neuroexcitation under extreme HBO<jats:sub>2<\/jats:sub>, limiting oxidant damage in the cerebellum and hippocampus, and likely lowering mitophagy flux and initiation of pCREB-initiated mitochondrial biogenesis.<\/jats:p>","DOI":"10.3389\/fnmol.2022.1062410","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T20:39:51Z","timestamp":1673383191000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["GAT inhibition preserves cerebral blood flow and reduces oxidant damage to mitochondria in rodents exposed to extreme hyperbaric oxygen"],"prefix":"10.3389","volume":"15","author":[{"given":"Ivan T.","family":"Demchenko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagir B.","family":"Suliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey Y.","family":"Zhilyaey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga S.","family":"Alekseeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana F.","family":"Platonova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Makowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude A.","family":"Piantadosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heath G.","family":"Gasier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"key":"ref1","first-page":"526","article-title":"CNS toxicity in closed-circuit oxygen diving: symptoms reported from 2527 dives","volume":"77","author":"Arieli","year":"2006","journal-title":"Aviat. 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