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Bondarenko, A; Svichar, N; Chesler, M.
Role of Na+-H+ and Na+-Ca2+ exchange in hypoxia-related acute astrocyte death.
Glia. 2005; 49(1):143-152 Doi: 10.1002/glia.20107
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Bondarenko Oleksandr
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Abstract:
Cultured astrocytes do not succumb to hypoxia/zero glucose for up to 24 h, yet astrocyte death following injury can occur within 1 h. It was previously demonstrated that astrocyte loss can occur quickly when the gaseous and interstitial ionic changes of transient brain ischemia are simulated: After a 20-40-min exposure to hypoxic, acidic, ion-shifted Ringer (HAIR), most cells died within 30 min after return to normal saline (i.e., "reperfusion"). Astrocyte death required external Ca2+ and was blocked by KB-R7943, an inhibitor of reversed Na+-Ca2+ exchange, suggesting that injury was triggered by a rise in [Ca2+]i. In the present study, we confirmed the elevation of [Ca2+]i during reperfusion and studied the role of Na+-Ca2+ and Na+-H+ exchange in this process. Upon reperfusion, elevation of [Ca2+]i was detectable by Fura-2 and was blocked by KB-R7943. The low-affinity Ca2+ indicator Fura-FF indicated a mean [Ca2+]i rise to 4.8+/-0.4 microM. Loading astrocytes with Fura-2 provided significant protection from injury, presumably due to the high affinity of the dye for Ca2+. Injury was prevented by the Na+-H+ exchange inhibitors ethyl isopropyl amiloride or HOE-694, and the rise of [Ca2+]i at the onset of reperfusion was blocked by HOE-694. Acidic reperfusion media was also protective. These data are consistent with Na+ loading via Na+-H+ exchange, fostering reversal of Na+-Ca2+ exchange and cytotoxic elevation of [Ca2+]i. The results indicate that mechanisms involved in pH regulation may play a role in the fate of astrocytes following acute CNS injuries.
Find related publications in this database (using NLM MeSH Indexing)
Acute Disease -
Animals -
Astrocytes - metabolism Astrocytes - pathology
Brain - metabolism
Calcium - metabolism
Calcium Signaling - drug effects Calcium Signaling - physiology
Cell Death - physiology
Cell Hypoxia - physiology
Cells, Cultured -
Enzyme Inhibitors - pharmacology
Fura-2 - analogs and derivatives Fura-2 - pharmacology
Hydrogen - metabolism
Hydrogen-Ion Concentration - drug effects
Hypoxia-Ischemia, Brain - metabolism
Ion Transport - physiology
Isotonic Solutions - pharmacology
Rats -
Reperfusion Injury - metabolism
Sodium - metabolism
Sodium-Calcium Exchanger - antagonists and inhibitors Sodium-Calcium Exchanger - metabolism
Sodium-Hydrogen Antiporter - antagonists and inhibitors Sodium-Hydrogen Antiporter - metabolism
Up-Regulation - drug effects Up-Regulation - physiology

Find related publications in this database (Keywords)
BCECF
Fura-2
Fura-FF
KB-87943
HOE-694
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