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Bondarenko, A; Chesler, M.
Rapid astrocyte death induced by transient hypoxia, acidosis, and extracellular ion shifts.
Glia. 2001; 34(2):134-142 Doi: 10.1002/glia.1048
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Leading authors Med Uni Graz
Bondarenko Oleksandr
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Abstract:
Death of astrocytes requires hours to days in injury models that use hypoxia, acidosis, or calcium paradox protocols. These methods do not incorporate the shifts in extracellular K(+), Na(+), Cl(-), and Ca(2+) that accompany acute brain insults. We studied astrocyte survival after exposure to hypoxic, acidic, ion-shifted Ringer (HAIR), with respective [Ca(2+)], [K(+)], [Na(+)], [Cl(-)], and [HCO(-)(3)] of 0.13, 65, 51, 75, and 13 mM (15% CO(2)/85% N(2), pH 6.6). Intracellular pH (pH(i)) was monitored with the fluorescent dye BCECF. Cell death was indicated by a steep fall in the pH-insensitive, 440-nm-induced fluorescence (F440) and was confirmed by propidium iodide staining. After 15-40-min HAIR exposure, reperfusion with standard Ringer caused death of most cultured (and acutely dissociated) astrocytes within 20 min. Cell death was not prevented if low Ca(2+) was maintained during reperfusion. Survival fell with increased HAIR duration, elevated temperature, or absence of external glucose. Comparable durations of hypoxia, acidosis, or ion shifts alone did not lead to acute cell death, while modest loss was noted when acidosis was paired with either hypoxia or ion shifts. Severe cell loss required the triad of hypoxia, acidosis, and ion shifts. Intracellular pH was significantly higher in HAIR media, compared with solutions of low pH alone or with low pH plus hypoxia. These results indicate that astrocytes can be killed rapidly by changes in the extracellular microenvironment that occur in settings of traumatic and ischemic brain injury.
Find related publications in this database (using NLM MeSH Indexing)
Acidosis - metabolism
Animals -
Astrocytes - cytology Astrocytes - metabolism
Calcium - pharmacokinetics
Cell Death - physiology
Cell Hypoxia - physiology
Cells, Cultured -
Cerebral Cortex - cytology
Coloring Agents -
Extracellular Space - metabolism
Glucose - pharmacology
Hydrogen-Ion Concentration -
Ischemic Attack, Transient - metabolism
Isotonic Solutions - chemistry
Potassium - pharmacokinetics
Propidium -
Rats -

Find related publications in this database (Keywords)
ischemia
BCECF
potassium
propidium iodide
extracellular pH
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