{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:17:25Z","timestamp":1770337045059,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2001,3,29]],"date-time":"2001-03-29T00:00:00Z","timestamp":985824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2001,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Exposure to hypoxic, acidic, ion\u2010shifted Ringer (HAIR) for 15\u201340 min has been shown to cause rapid astrocyte death upon reperfusion with normal media. The ion shifts of the HAIR solution included a rise in extracellular K<jats:sup>+<\/jats:sup> (e.g., [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>) and a fall in [Na<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>, [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>o<\/jats:sub>, and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>, characteristic of ischemic\u2010traumatic brain insults. We investigated the ionic basis of the HAIR\u2010induced injury. After HAIR exposure, reperfusion in 0 Ca<jats:sup>2+<\/jats:sup>\/EGTA media completely protected astrocytes. Preincubation of cells in BAPTA\u2010AM ester was also protective, indicating that the injury was triggered by Ca<jats:sup>2+<\/jats:sup> influx during reperfusion. Neither nimodipine, CNQX, APV, nor TTX reduced injury. Astrocyte death could be blocked by 100 \u03bcM Ni<jats:sup>2+<\/jats:sup> or 100 \u03bcM benzamil, suggesting involvement of Na<jats:sup>+<\/jats:sup>\u2013Ca<jats:sup>2+<\/jats:sup> exchange. KB\u2010R7943, which preferentially inhibits reverse Na<jats:sup>+<\/jats:sup>\u2013Ca<jats:sup>2+<\/jats:sup> exchange, also protected astrocytes. Elevation of [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub> was not necessary for astrocyte death. However, when [Na<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub> was maintained at 151 mM throughout the HAIR protocol, cell death was markedly reduced. We postulate that [Na<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub> shifts aid reversal of Na<jats:sup>+<\/jats:sup>\u2013Ca<jats:sup>2+<\/jats:sup> exchange by favoring cytosolic Na<jats:sup>+<\/jats:sup> loading. Possible means of astrocytic Na<jats:sup>+<\/jats:sup> accumulation are discussed. 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